THE WELCH COMPANY
440 Davis Court #1602
San Francisco, CA 94111-2496
415 781 5700
rodwelch@pacbell.net


S U M M A R Y


DIARY: October 17, 2008 07:12 AM Friday; Rod Welch

Millie typed up the Consent document for the Sunitinib clinical trial.

1...Summary/Objective
2...Sunitinib Clinical Study Consent Data Entry Command Control Record
........Cyclophosphamide and Methotrexate Given with Sunitinib
............Adriamycin - Duxorubicin - Chemotherapy for Breast Cancer
........Metronomic Low Dose Increase Frequency - Daily
........Circulating tumor cells (CTCs) Blood Tests
........Circulating endothelial Cells (CEC) Blood Tests
........CTC and CEC Targeted Blood Cells Evaluate Treatments
........Targeted Treatment Prevents New Tumor Blood Vessels Developing
............Questions
........Dose Study Effects Changing Levels Discover Optimal Treatment
3...Blood Tests CBC and Chemestry Levels
4...Side Effects Sunitinib
5...Sunitinib Side Effects...
6...Side Effects Cyclophosphamide (Cytoxan)
7...Cyclophosphamide Side Effects (Cytoxan)
8...Cytoxan Side Effects (Cyclophosphamide)
9...Side Effects Cytoxan (Cyclophosphamide)
10...Methotrexate Side Effects
11...Side Effects Methotrexate
12...Side Effects Radiation
13...Radiation Side Effects
14...Side Effects CT Tests
15...CT Tests Side Effects
16...Treatment Protocol Sunitinib and Cyclophosphamide Taken Everyday
17...Methotrexate Taken 2 Days Consecutively Each Week of 3 Week Cycles

ACTION ITEMS.................. Click here to comment!

1...Does Millie's favorable experience with cetuximab
2...Nupogen - how will treatments affect blood counts, and
3...How will changing dose levels be implemented?
.....ppears conflicting with the protocol calling for methrotresate to

CONTACTS 

SUBJECTS
Sunitinib Clinical Study Drug Trial Consent  Dcument 080828 Data Ent

0903 -
0903 -    ..
0904 - Summary/Objective
0905 -
090501 - Follow up ref SDS 15 0000.
090502 -
090503 -
090504 -
090506 -  ..
0906 -
0907 -
0908 - Progress
0909 -
090901 - Sunitinib Clinical Study Consent Data Entry Command Control Record
090902 -
090903 - Follow up ref SDS 15 215I, ref SDS 14 J38U.
090904 -
090905 - Yesterday, Glenna, the coordinator, for the Sunitinib study, delivered
090906 - a printed Consent document, ref OF 1 0001, to Millie while she was
090907 - getting treatment in the Infusion Clinic for cancer with the cetuximab
090908 - clinical study. ref SDS 13 KV4O
090910 -  ..
090911 - Millie's letter to Doctor Rugo last night confirmed understandings on
090912 - the work plan for changing treatments.  She asked for the computer
090913 - file on the Consent document, in order to save time for data entry
090914 - typing the computer file for case management. ref SDS 14 J39T  The
090915 - doctor's letter responding shortly after midnight, indicated she would
090916 - check with the study sponsor about submitting the computer file on the
090917 - Consent document. ref SDS 15 6J3P
090919 -  ..
090920 - UCSF did not have time to respond.
090921 -
090922 -        [On 081031 Glenna proposed sending via email the signature page
090923 -        of the Consent document in a computer file. ref SDS 24 CC3O
090925 -  ..
090926 - Millie entered the consent document into the record for case
090927 - management. ref OF 1 0001
090929 -  ..
090930 - Typing the document, and proof reading for accuracy took about 4.5
090931 - hours, so we could not go hiking today.
090933 -  ..
090934 - Review of the consent form shows...
090935 -
090936 -    1.  Clinical study document dated 080828. ref OF 1 WF4M
090937 -
090938 -        Phase I/II study of sunitinib (SU11248) in combination with
090939 -        metronomic cyclophosphamide and methotrexate for patients with
090940 -        metastatic breast cancer. ref OF 1 LG3N
090942 -         ..
090943 -        During the meeting at UCSF yesterday, the doctor explained
090944 -        this is a phase 1/II study, which she feels Millie may qualify
090945 -        for participation.  The meaning of Phase I/II was not
090946 -        explained at UCSF.
090947 -
090948 -           [On 081018 Doctor Stritter speaking at a Wellness Community
090949 -           event related her research showing promising potential for
090950 -           Millie's treatment with Sunitinib, ref SDS 16 PQ6X; Gwen
090951 -           seemed to indicate the Phase I/II status of the study has
090952 -           yielded good results, which have not been published.
090953 -           ref SDS 16 OR6J
090955 -            ..
090956 -           [On 081019 Millie sent a letter to the primary care
090957 -           physician submitting Doctor Stritter's favorable comments on
090958 -           the sunitinib clinical trial for treatting Millie's 5th
090959 -           relapse of IBC. ref SDS 17 D13Q
090961 -            ..
090962 -           [On 081021 Consent document for Sunitinib clinical study
090963 -           sent to primary care physician to prepare for meeting on
090964 -           081024. ref SDS 18 W83I
090966 -         ..
090967 -        The doctor glanced through the medical chart and drew a
090968 -        conclusion that Millie's treatment history meets the study
090969 -        critieria.  Since Millie has been in treatment for 7 years, she
090970 -        has received most of the common treatments for breast cancer.
090971 -        Therefore, options for treatment are limited.  The doctor
090972 -        explained a strategy of reserving common treatments until other
090973 -        options have been exhausted.  This is accomplished by trying
090974 -        new treatments being tested in clincial trials.
090976 -         ..
090977 -        On 061201 the primary care physician at Kaiser seemed to
090978 -        indicate Millie has only 2 more common drugs available to treat
090979 -        her cancer, Navelbine and Gemzar. ref SDS 4 ZZ9N  On 061208 the
090980 -        doctor prescribed Navelbine, and scheduled treatment to start
090981 -        on 070105. ref SDS 5 N96O  On 070105, the doctor changed the
090982 -        prescription to the clinical trial at UCSF for cetuximab and
090983 -        Carboplatin. ref SDS 6 PK7L
090985 -         ..
090986 -        Doctor Rugo explained yesterday that a clinical trial for
090987 -        another drug will start in about 4 months.  She seemed to
090988 -        suggest today, that based on favorable response of 1 patient,
090989 -        Millie might experience some recovery from cancer with the
090990 -        Sunitinib treatment, at least for 4 months until the next trial
090991 -        will available.
090993 -         ..
090994 -        Another strategy is the work plan on 081016 testing for triple
090995 -        negative status change, with the biopsy ordered to evaluate
090996 -        progression of cancer in the left supraclavicular. ref SDS 14
090997 -        J36R  If the biopsy shows Millie's status has changed, from
090998 -        triple negative to at least HER2 positive, then there would be
090999 -        more drugs available to treat Millie.
091001 -         ..
091002 -    2.  Doctor Rugo is the principle investigator for the study.
091003 -        ref OF 1 B43P
091005 -         ..
091006 -        Phase I study - evidently this is the first time this
091007 -        combination of drugs has been tried.
091009 -         ..
091010 -    3.  Sunitinib clinical study rationale...
091011 -
091012 -        The purpose of this study is to test the safety of sunitinib, a
091013 -        new cancer drug, at different dose levels.  Sunitinib has
091014 -        already been approved by the Food and Drug Administration for
091015 -        the treatment of kidney cancer and a rare kind of sarcoma.
091016 -        ref OF 1 008N
091017 -
091019 -         ..
091020 -        Cyclophosphamide and Methotrexate Given with Sunitinib
091021 -
091022 -        Sunitinib will be given with two other chemotherapy drugs,
091023 -        cyclophosphamide and methotrexate.  These two drugs are already
091024 -        approved for the treatment of breast cancer. ref OF 1 004O
091025 -
091026 -            [On 081223 Millie's letter to medical team commended Doctor
091027 -            Rugo for engineering strong recovery with sunitinib,
091028 -            ref SDS 40 BV4T; Millie cited discussion with Doctor
091029 -            Johnson at Kaiser today on 081219 explaining competing
091030 -            values of patient health and getting test data, ref SDS 40
091031 -            BV6R; Millie advised the medical team of preference to
091032 -            maintain sunitinib dose amount that has been effective, and
091033 -            to reduce dose or eliminate treatment with cyclophosphamide
091034 -            that may not be effective, and which may be causing severe
091035 -            adverse chemotherapy side effects. ref SDS 40 BW3V
091037 -  ..
091038 - Research shows cyclophosphamide is the generic name for Cytoxan...
091039 -
091040 -              http://www.medicinenet.com/cyclophosphamide/article.htm
091042 -  ..
091043 - This particular source presents no correlation between
091044 - cyclophosphamide (Cytoxan), and heart damage that can be assessed with
091045 - a Muga test.
091047 -  ..
091048 - A recent article published by About.com a Breast Care Internet source,
091049 - and written by Pam Stephan dated 080612....
091050 -
091051 -            Adriamycin - Duxorubicin - Chemotherapy for Breast Cancer
091053 -  ..
091054 - Ms Stephan describes a correlation between Adriamycin (duxorubicin)
091055 - and heart damage, and further recommends Muga testing to monitor for
091056 - problems...
091057 -
091058 -              http://breastcancer.about.com/od/chemotherapydrugs/p/adriamycin.htm
091060 -  ..
091061 - The article says in part...
091062 -
091063 -            Because this drug can cause heart problems, you should
091064 -            have a MUGa scan, LVEF (leftventricular failure) test or
091065 -            heart health evaluation done before starting treatment.
091066 -            This baseline exam will be used to compare with your heart
091067 -            function during and, after treatment.
091069 -  ..
091070 - The sunitinib study using cyclophosphamide (Cytoxan), therefore
091071 - appears to present no elevated threat for heart damage that requires
091072 - Muga testing.
091074 -  ..
091075 - Sunitinib study consent document continues...
091077 -         ..
091078 -        Metronomic Low Dose Increase Frequency - Daily
091079 -
091080 -        Cyclophosphamide and methotrexate will be given daily, in lower
091081 -        doses than are typically used to treat patients with breast
091082 -        cancer.  This dosing schedule is called "metronomic."
091083 -        ref OF 1 6X8F
091085 -  ..
091086 - Seems to conflict with the explanation below that cyclophosphamide
091087 - will be taken daily, but methotrexate will be taken only twice a week
091088 - on consecutive days, and on those days, will be taken twice each day.
091089 - ref SDS 0 Q14K
091091 -  ..
091092 - Sunitinib study consent document continues...
091093 -
091094 -        Unlike standard cancer treatment, where large doses of
091095 -        chemotherapy drugs are given in a cyclical fashion, metronomic
091096 -        dosing involves giving low doses of chemotherapy every day,
091097 -        without a break.  In animal studies, metronomic chemotherapy
091098 -        can be effective at treating tumors that do not respond to
091099 -        standard, cyclical chemotherapy. ref OF 1 QY8K
091100 -
091102 -         ..
091103 -        Circulating tumor cells (CTCs) Blood Tests
091104 -        Circulating endothelial Cells (CEC) Blood Tests
091105 -        CTC and CEC Targeted Blood Cells Evaluate Treatments
091106 -        Targeted Treatment Prevents New Tumor Blood Vessels Developing
091107 -
091108 -
091109 - Sunitinib study consent document continues...
091110 -
091111 -        We believe sunitinib in combination with metronomic dose
091112 -        cyclophosphamide and methotrexate targets new blood vessels
091113 -        that are formed by tumors, and that damaging these blood
091114 -        vessels or preventing the new tumor blood vessels from
091115 -        developing may be an effective way to treat cancer. ref OF 1
091116 -        006S
091118 -         ..
091119 -        Blood draw monitors effects of treatment on the levels of
091120 -        circulating tumor cells (CTCs) and circulating endothelial
091121 -        cells (CECs).  We are looking at these levels to see if they
091122 -        may help us predict which patients will have a response to the
091123 -        study treatment. ref OF 1 MI9L
091125 -  ..
091126 - Study will "target" CTC and CEC blood cells to help predict repsonse
091127 - to treatment.
091128 -
091129 -           [On 081018 Doctor Stritter speaking at a Wellness Community
091130 -           event related her research showing promising potential for
091131 -           Millie's treatment with Sunitinib. ref SDS 16 IT8V
091133 -            ..
091134 -           [On 081019 Millie sent a letter to the primary care
091135 -           physician submitting Doctor Stritter's favorable comments on
091136 -           the sunitinib clinical trial for treatting Millie's 5th
091137 -           relapse of IBC. ref SDS 17 D13Q
091139 -            ..
091140 -           [On 081024 primary care phsyician approves Millie for
091141 -           treatment at UCSF with sunitinib metronomic protocol,
091142 -           ref SDS 21 XZ8W, because Millie's advance condtion of 5th
091143 -           relapse requires double agent drugs, and Kaiser only has
091144 -           "old technology" single agent treatments left to treat
091145 -           Millie's 5th relapse, and further, becauser Kaiser's
091146 -           experience with sunitinib indicates this can be effective
091147 -           for Millie. ref SDS 21 ER4I
091149 -            ..
091150 -           [On 081125 letter to medical team submitting agenda for
091151 -           meeting the next day reports evident response to treatment
091152 -           after 2 weeks with sunitinib clinical study at UCSF.
091153 -           ref SDS 29 XX3W
091155 -            ..
091156 -           [On 081202 letter to medical team reports findings from
091157 -           examination on 081126 of recovery from IBC; and days later
091158 -           there was significant increased recovery. ref SDS 30 AS6U
091160 -            ..
091161 -           [On 081223 Millie's letter to medical team commended Doctor
091162 -           Rugo for engineering strong recovery with sunitinib,
091163 -           ref SDS 40 BV4T; Millie cited discussion with Doctor Johnson
091164 -           at Kaiser today on 081219 explaining competing values of
091165 -           patient health and getting test data, ref SDS 40 BV6R;
091166 -           Millie advised the medical team of preference to maintain
091167 -           sunitinib dose amount that has been effective, and to reduce
091168 -           dose or eliminate treatment with cyclophosphamide that may
091169 -           not be effective, and which may be causing severe adverse
091170 -           chemotherapy side effects. ref SDS 40 BW3V
091172 -  ..
091173 - "Targeted cancer treatment aligns with Doctor Rugo's discussion
091174 - yesterday at UCSF, and confirmed in a letter sent to the primary care
091175 - physician at Kaiser. ref SDS 14 J35X
091176 -
091177 -            Questions
091178 -
091179 -            1.  Does Millie's favorable experience with cetuximab
091180 -                "targeted" drug effect prospects for effectiveness of
091181 -                Sunitinib "targeted" drug?
091183 -                 ..
091184 -                Does progression of disease with "targeted" cetuximab
091185 -                technology, determined on Thursday 081016, make it
091186 -                likely "targeted" Sunitinib cannot be effective?
091187 -
091188 -                    [On 081018 Doctor Gwen Stritter commented during
091189 -                    presentation at Wellness Communitiy event on cancer
091190 -                    treatment and quality of life, that Sunitinib
091191 -                    "targets" cancer on a broader scale than cetuximab.
091192 -                    ref SDS 16 IT8V
091194 -                     ..
091195 -                    [On 081023 agenda for meeting at Kaiser review
091196 -                    questions on sunitinib clinical study. ref SDS 19
091197 -                    L45S
091199 -  ..
091200 - Sunitinib study consent document continues...
091202 -         ..
091203 -        Dose Study Effects Changing Levels Discover Optimal Treatment
091204 -
091205 -        We want to find out what the optimal dose of sunitinib is to
091206 -        use with these other drugs.  We also want to learn more about
091207 -        what effects, good and/or bad, that this combination of drugs
091208 -        has on you and your breast cancer. ref OF 1 1J4F
091210 -                 ..
091211 -            2.  Nupogen - how will treatments affect blood counts, and
091212 -                need for continuing Neupogen treatments?
091214 -                 ..
091215 -            3.  How will changing dose levels be implemented?
091216 -
091217 -                Is there a published protocol to start with a specified
091218 -                dose, and continue for a specified period, then change
091219 -                to a bigger or smaller dose?
091221 -                 ..
091222 -                If the patient is doing well at the current dose, will
091223 -                the study experiement by reducing the dose to reduce
091224 -                side effects and cost, to find the minimum level of
091225 -                treatment that yields recovery?
091227 -                 ..
091228 -                If the patient shows progression of disease, will dose
091229 -                be increased to improve results?
091231 -                 ..
091232 -                Or, will dose be increased regardless of response in
091233 -                order to test for tolerance and side effects?
091235 -  ..
091236 - Sunitinib study consent document continues...
091237 -
091238 -    4.  Participants 6 - 18 Phase I Study
091239 -
091240 -        Between 6 and 18 people will take part in this study.  At the
091241 -        beginning of the study, 3 patients will be treated with a low
091242 -        dose of the drug.  If this dose does not cause bad side
091243 -        effects, it will slowly be made higher as new patients take
091244 -        part in the study.  You can ask your study doctor what dose you
091245 -        will receive.  A total of 18 patients is the most that would be
091246 -        able to enter the study.  This study will only be open at the
091247 -        UCSF Comprehensive Cancer Center. ref OF 1 LG45
091249 -  ..
091250 - During the meeting yesterday, the doctor seemed to say 1 patient has
091251 - responded well for 4 months.
091252 -
091253 -            4.  How many patients are currently in the study?
091254 -
091255 -            5.  When did the study start?
091257 -                 ..
091258 -            6.  Have any patients dropped out of the study due to side
091259 -                effect?  If so, what side effects?
091261 -                 ..
091262 -            7.  Have any patients dropped out of the study due to
091263 -                progression of disease and/or side effects?
091265 -                 ..
091266 -            8.  Are different doses tried on each patient, or do all
091267 -                patients get the same dose for the same period of time?
091269 -                 ..
091270 -            9.  Will the dose be increased based of results showing
091271 -                favorable response?
091273 -                 ..
091274 -           10.  Is the dose set by the stage of the test, or based on
091275 -                the condition of the patient, e.g., would a patient
091276 -                with a more severe condition be started with a high
091277 -                dose than an patient with less severe cancer?
091279 -                 ..
091280 -                Will the dose be higher for patients with better
091281 -                fitness to assess tolerance for high dose levels?
091282 -
091283 -
091285 -  ..
091286 - Blood Tests CBC and Chemestry Levels
091287 -
091288 -
091289 - Sunitinib study consent document continues...
091290 -
091291 -    5.  Blood draws and chemestry levels start each new cycle
091292 -
091293 -        Blood drawing (venipuncture);  A blood sample will be drawn by
091294 -        inserting a needle into a vein in your arm.  About 4 teaspoons
091295 -        will be taken to check blood counts and chemistry levels.
091296 -        ref OF 1 LH3P
091297 -
091298 -            [On 081029 CBC blood test entered in UCSF work plan for
091299 -            Millie to start treatment in sunitinib clinical study.
091300 -            ref SDS 23 1H5G
091302 -             ..
091303 -            [On 081027 UCSF added urinalysis to laboratory tests for
091304 -            Millie to start treatment in the sunitinib clinical study.
091305 -            ref SDS 22 309F
091307 -             ..
091308 -            [On 081031 Glenna advises during a telephone call that
091309 -            the Consent documents for the sunitinib clinical study
091310 -            do not specify urnialysis. ref SDS 24 4G6N
091312 -         ..
091313 -        Blood drawing (venipuncture):  At the start of each new cycle
091314 -        of treatment, a blood sample will be drawn by inserting a
091315 -        needle into a vein in your arm to measure your blood counts and
091316 -        chemistry levels.  Each sample will be approximately 2
091317 -        teaspoons, a total of about 4 tablespoons will be drawn for the
091318 -        whole study however    some subjects may have more total blood
091319 -        drawn if they receive study treatment for more than 5 cycles.
091320 -        ref OF 1 MI7S
091322 -            ..
091323 -           Questions...
091324 -
091325 -           11.  What is the "cycle" for this study?
091327 -  ..
091328 - The first cycle is 15 days or 37 days?? ref OF 1 YS4J,
091329 -
091330 -               [On 081107 Millie gets first lab work at UCSF for the
091331 -               sunitinib clinical study. ref SDS 26 1K7H
091333 -  ..
091334 - Subsequent cycles are 21 days. ref OF 1 Y345
091336 -  ..
091337 - Sunitinib study consent document continues...
091338 -
091339 -           12.  How many cycles are patients expected to get, i.e.,
091340 -                4, 5, 10, 100.  Will side effects accumulate with each
091341 -                cycle?
091343 -                 ..
091344 -           13.  Blood draws - can they use Millie's port?
091345 -
091346 -                Will the amount of blood be comparable to current blood
091347 -                draws every 4 weeks in the cetuximab Carboplatin study?
091349 -                 ..
091350 -                If more blood will be drawn for Sunitinib, how will
091351 -                this effect energy, quality of life?
091353 -  ..
091354 - Sunitinib study consent document continues...
091355 -
091356 -    6.  CT scan every 6 weeks...
091357 -
091358 -        Initial CT test to evaluate taking part in the study.
091359 -        ref OF 1 LH37
091361 -         ..
091362 -        You will have a computer tomography (CT) scan of your chest/
091363 -        abdomen/ pelvis every 6 weeks to see what the effects the study
091364 -        treatment is having on your breast cancer. ref OF 1 MI83
091365 -
091366 -            [...below, in the record today 081017, side effects of CT
091367 -            tests are presented.
091369 -             ..
091370 -            [On 081024 primary care physician reviews Consent document
091371 -            for sunitinib clinical study and orders CT test to enable
091372 -            Millie to get treatment of IBC. ref SDS 21 XZ9P
091374 -         ..
091375 -        Get routine CT scans every other cycle (more if your doctor
091376 -        tells you to). ref OF 1 0359
091378 -  ..
091379 - Since cycles seem to be 21 days, which is 3 weeks, then getting CT
091380 - tests every other cycle makes 6 weeks.
091381 -
091382 -           Questions...
091383 -
091384 -           14.  Does Millie's patient history showing no distant
091385 -                metastasis, except very minor nodes in right axilla,
091386 -                and now possibly in left supraclavicular, and no
091387 -                actual tumors, enable reducing frequency of CT tests
091388 -                to an 8 or 12 week schedule?
091390 -         ..
091391 -    7.  Echocardiogram:
091392 -
091393 -        Screening procedures require an echocardiogram to make sure
091394 -        your heart is functioning properly.  This examination uses
091395 -        sound waves to make pictures of your heart, which helps
091396 -        determine how well your heart pumps blood.  You will be asked
091397 -        to lie on your left side while a technician places a probe with
091398 -        gel on your chest to creart images of your heart to determine
091399 -        the function and size.  The procedure is done in the cardiology
091400 -        department and will take approximate 60 minutes. ref OF 1 LH53
091401 -
091402 -            [On 081024 primary care physician reviews Consent document
091403 -            for sunitinib clinical study and orders echocardiogram on
091404 -            081110 0930 to enable Millie to get treatment of IBC.
091405 -            ref SDS 21 XZ9S
091407 -             ..
091408 -            [On 081110 echocardiogram test of heart; initial
091409 -            indications Millie has strong heart that permits low blood
091410 -            pressure, no evident signs of enlarged right ventricle, nor
091411 -            enlarged heart. ref SDS 27 WL63
091412 -
091413 -
091414 -
0915 -

SUBJECTS
Default Null Subject Account for Blank Record

1003 -
100401 -  ..
100402 - Side Effects Sunitinib
100403 - Sunitinib Side Effects...
100404 -
100405 -
100406 -    8.  Likely between (10-50%): Sunitinib...
100407 -
100408 -        1.  Fatigue, which can limit your activities
100410 -  ..
100411 - This could be a sigificant side effect if Millie cannot continue with
100412 - regular exercise, shown by patient history on 081014. ref SDS 12 8G5M
100414 -  ..
100415 - Research on the Internet found...
100416 -
100417 -            Doublecheckmd
100418 -
100419 -              http://doublecheckmd.com/EffectsDetail.do?dname=Sutent&sid=75586&eid=2089
100420 -
100421 -            Sutent (sunitinib) - Peripheral neuropathy
100422 -            Multum version: 135.0 (Nov 17, 2008)
100424 -             ..
100425 -            Lack of energy/fatigue occurs in less than 74% of people
100426 -            Muscle weakness in less than 22% of people
100427 -
100428 -               [On 081024 1150 primary care physician related
100429 -               experience treating patients with sunitinib at Kaiser,
100430 -               other than for breast cancer, shows some patients suffer
100431 -               side effects of fatigue and neuropathy; the dose levels
100432 -               may different from what Millie will get at UCSF, and
100433 -               Millie's good physicial condition from vigorous exercise
100434 -               will help minimize these effects in Millie's case.
100435 -               ref SDS 20 O668
100437 -                ..
100438 -               [On 090101 Millie very difficult hiking Lafayette
100439 -               because leg muscles very weak, and neuropathy in feet
100440 -               and toes.
100442 -  ..
100443 - Exercise may be a factor helping slow spread of cancer, shown by
100444 - stable CA 15-3 for 3 months, and stable adenopathy reported in CT
100445 - tests for 6 months, reported on 081016. ref SDS 13 VJ4G
100447 -  ..
100448 - Sunitinib Side Effects - Likely (10-50%) continue...
100449 -
100450 -        2.  High blood pressure, which may require need for medication
100451 -        3.  Diarrhea
100452 -        4.  Nausea
100453 -        5.  Loss of appetite
100454 -        6.  Upset stomach
100455 -        7.  Vomiting
100456 -        8.  Increase lipase level (a digestive enzyme)
100457 -        9.  Yellowing of the skin
100458 -       10.  Hair color changes
100459 -       11.  Headache
100460 -       12.  Shortness of breath
100461 -       13.  Inflammation of mucous membranes (including mouth sores)
100462 -       14.  Altered taste
100463 -       15.  Swelling
100464 -       16.  Constipation
100465 -       17.  Muscle aches
100466 -             ..
100467 -       18.  Joint/back pain
100468 -       19.  Dermatitis
100470 -         ..
100471 -    9.  Less Likely (1-10%): Sunitinib
100472 -
100473 -        1.  Nosebleeds
100474 -
100475 -                [On 081217 Millie reported minor nosebleed.
100476 -                ref SDS 35 ZF5F
100478 -                 ..
100479 -                [On 081217 Millie suffered moderate nosebleed lasted
100480 -                about an hour. ref SDS 36 ZF5F
100482 -             ..
100483 -        2.  Insomnia
100484 -        3.  Cough
100485 -        4.  Fever
100486 -        5.  Increased eye tearing
100488 -             ..
100489 -        6.  Increased heart muscle enzyme levels
100490 -        7.  Decreased heart muscle function
100492 -  ..
100493 - Millie has some patient history related to cardio pulmonary issues...
100494 -
100495 -            a.  irregular heart beat diagnosed in an EKG test during
100496 -                surgery for reexcision on 020327. ref SDS 1 QF6L
100498 -                 ..
100499 -            b.  pulmonary embolism diagnosed CT test on 041103 reviewed
100500 -                at Kaiser on 041104. ref SDS 2 QP6S
100502 -                 ..
100503 -            c.  pulmonary embolism recurrance CT test at Kaiser on
100504 -                061012. ref SDS 3 294Q
100506 -                 ..
100507 -            d.  enlarged right ventricle (cor pulmonale) diagnosed CT
100508 -                test at Kaiser 061012. ref SDS 3 7E5L
100510 -                 ..
100511 -            e.  slightly enlarged heart diagnosed CT test on 071210
100512 -                reviewed on 071213. ref SDS 8 SR5I
100514 -                 ..
100515 -            f.  Elevated pulse for several hours reported during hiking
100516 -                on 081012. ref SDS 11 4I8M
100518 -  ..
100519 - Significance of this patient history is not clear in the record.
100520 -
100521 -                    [On 081105 Millie notified that primary care
100522 -                    physician orders Muga test for heart damage prior
100523 -                    to starting sunitinib clinical study that has some
100524 -                    heart related side effects. ref SDS 25 WO72
100526 -                     ..
100527 -                    [On 090109 Millie's letter to medical team request
100528 -                    Kaiser to order EKG. ref SDS 45 UF4V
100530 -                     ..
100531 -                    [On 090112 Millie got the CT test at Kaiser.
100532 -                    ref SDS 46 DB5I
100534 -                     ..
100535 -                    [On 090116 Glenna called and requested submission
100536 -                    of results for the EKG test to UCSF. ref SDS 47
100537 -                    JY9G
100538 -
100540 -  ..
100541 - Sunitinib Side Effects - Less Likely (1-10%) continue...
100542 -
100543 -        8.  Increased levels of liver enzymes (may indicate liver
100544 -            damage)
100545 -
100546 -        9.  Decreased kidney function
100548 -             ..
100549 -       10.  Decreased white blood cells infection fighting cells;  this
100550 -            problem may lead to increased risk of infection)
100552 -             ..
100553 -       11.  Decreased red blood cells (may make you feel tired or short
100554 -            of breath
100556 -  ..
100557 - Millie has had recent problems holding blood counts with chemotherapy;
100558 - Taking Nupogen and increased exercise have stabalized blood counts in
100559 - recent months, reported yesterday on 081016. ref SDS 13 OK67
100560 -
100561 -                    [On 081205 Millie blood counts low from labs at
100562 -                    Kaiser on 081203 were reported to medical team.
100563 -                    ref SDS 31 TT8P
100565 -                     ..
100566 -                    [On 081218 labs at UCSF for examination starting
100567 -                    2nd cycle of sunitinib protocol show CBC blood
100568 -                    counts again very low, ref SDS 37 075H, with
100569 -                    platelets 67, ref SDS 37 7Z6N, attributed for
100570 -                    causing new sunitinib side effect of nosebleed,
100571 -                    ref SDS 38 GF4S, and NEUTS 0.74 have again fallen
100572 -                    substantially, ref SDS 37 QY6H; as a result
100573 -                    treatment regimen changed; all treatment was paused
100574 -                    for 7 days until 081226; Methotrexate ended
100575 -                    entirely; consideration will be made to reduce dose
100576 -                    for sunitinib. ref SDS 38 GF4V
100578 -                     ..
100579 -                    [On 081230 case study reviews delimma balancing
100580 -                    treatments and maintaining blood counts.
100581 -                    ref SDS 42 I87N
100583 -                     ..
100584 -                    [On 090108 NEUTS 0.87 below 1.50 safe level, labs
100585 -                    at UCSF start 3rd cycle sunitinib,
100586 -                    ref SDS 44 QY6H
100588 -                     ..
100589 -                    [On 090109 Millie's letter to medical team confirms
100590 -                    work plan UCSF prescribes Neupogen on 090109 and
100591 -                    090110, and treatment with cyclophosphamide paused
100592 -                    for 1 week until blood counts increase.
100594 -             ..
100595 -       12.  Decreased platelet count (may lead to increased bleeding)
100596 -
100597 -                    [On 081205 Millie blood counts low platelets 109
100598 -                    well below 140 from labs at Kaiser on 081203 were
100599 -                    reported to medical team. ref SDS 31 TT8P
100600 -
100601 -                    [On 081210 follow up blood test shows platelets 67,
100602 -                    about 60% below the target range of 104.
100603 -                    ref SDS 32 DM6J
100605 -                     ..
100606 -                    [On 081211 Millie letter to medical team asks about
100607 -                    effects on health care with platelets falling below
100608 -                    60% of the target range. ref SDS 33 S28P
100610 -                     ..
100611 -                    [On 081218 labs at UCSF for examination starting
100612 -                    2nd cycle of sunitinib protocol show CBC blood
100613 -                    counts again very low, ref SDS 37 075H, with
100614 -                    platelets 67, ref SDS 37 7Z6N, attributed for
100615 -                    causing new sunitinib side effect of nosebleed,
100616 -                    ref SDS 38 GF4S, and NEUTS 0.74 have again fallen
100617 -                    substantially, ref SDS 37 QY6H; as a result
100618 -                    treatment regimen changed; all treatment was paused
100619 -                    for 7 days until 081226; Methotrexate ended
100620 -                    entirely; consideration will be made to reduce dose
100621 -                    for sunitinib. ref SDS 38 GF4V
100623 -                     ..
100624 -                    [On 081220 Millie received 2 treatments with
100625 -                    Neuopgen. ref SDS 39 P73J
100627 -                     ..
100628 -                    [On 081226 platelets increased to 187 well above
100629 -                    140 safe level, ref SDS 41 DM6J,
100631 -                     ..
100632 -                    [On 081230 case study reviews delimma balancing
100633 -                    treatments and maintaining blood counts.
100634 -                    ref SDS 42 I87N
100636 -                     ..
100637 -                    [On 090108 platelets 175 still above 140 safe
100638 -                    level, labs at UCSF start 3rd cycle sunitinib.
100639 -                    ref SDS 44 7Z6N
100640 -
100642 -             ..
100643 -       13.  Neuropathy peripheral
100644 -
100645 -            This is not listed in the UCSF study consent document.
100647 -  ..
100648 - Research on the Internet found...
100649 -
100650 -            Doublecheckmd
100651 -
100652 -              http://doublecheckmd.com/EffectsDetail.do?dname=Sutent&sid=75586&eid=2089
100653 -
100654 -            Sutent (sunitinib) - Peripheral neuropathy
100655 -            Multum version: 135.0 (Nov 17, 2008)
100657 -             ..
100658 -            Sutent may cause peripheral neuropathy in 10% of people.
100659 -            This drug may also cause the following symptoms that are
100660 -            related to peripheral neuropathy:
100661 -
100662 -            a.  Hand-Foot syndrome - may cause redness, tenderness,
100663 -                numbness, tingling, discomfort, or peeling of the palms
100664 -                and soles in less than 14% of people
100665 -
100666 -                    [On 081216 Millie reported rising peripheral
100667 -                    neuropathy discomfort in feet and toes. ref SDS 34
100668 -                    HY8M
100670 -                     ..
100671 -                    [On 090101 Millie very difficult hiking Lafayette
100672 -                    because leg muscles very weak, and neuropathy in
100673 -                    feet and toes. ref SDS 43 3E4K
100674 -
100676 -  ..
100677 - There is a lot of research indicating that cyclophosphamide does not
100678 - increase peripheral neuropathy, except high dose of cyclophosphamide
100679 - may cause peripheral neuropathy, and it appears that in some cases
100680 - cyclophosphamide may treat some forms of neuropathy.
100681 -
100682 -            Systemic Lupus Erythematosus (SLE) presenting with
100683 -            peripheral neuropathy: A rare occurrence
100684 -            Vandana Mehta Rai MD 1, SD Shenoi MD 1, Sathish B Pai MD
100685 -            1, Vinod Joseph Choondlal MD 2,
100686 -            Dermatology Online Journal 11 (3): 43
100688 -               ..
100689 -              http://dermatology.cdlib.org/113/letters/neuropathy/shenoi.html
100691 -             ..
100692 -            1.  Dept of Skin & STD, Kasturba Medical College, Manipal
100693 -            576104, Karnataka, India. vandanamht@yahoo.com2.  Dept of
100694 -            Neurology, Kasturba Medical College, Manipal 576104,
100695 -            Karnataka, India
100697 -             ..
100698 -            2005 Dermatology Online Journal
100700 -             ..
100701 -            Neuropathies are a prominent feature of systemic
100702 -            vasculitides.  The immediate cause of the vasculitic
100703 -            neuropathies is inflammation and occlusion of the vasa
100704 -            nervosum resulting in ischemia of the peripheral nerve.
100705 -            Peripheral neuropathy occurs in 6-21 percent of patients
100706 -            with SLE and can manifest as cranial neuropathy or as
100707 -            polyneuritis. Mononeuritis multiplex can sometimes be the
100708 -            initial presentation of SLE[1].  Confirmation of diagnosis
100709 -            is by nerve biopsy and nerve conduction studies.
100711 -             ..
100712 -            Although the mainstay of treatment of peripheral neuropathy
100713 -            is corticosteroids, resistant cases may need
100714 -            cyclophosphamide, azathioprine or plasma exchange.  Pulse
100715 -            cyclophosphamide has been successfully tried in two cases
100716 -            of mononeuritis multiplex in SLE[2] and in cases of
100717 -            neuropsychiatric lupus with peripheral neuropathy [3].
100718 -            This case has been reported to highlight the importance of
100719 -            cyclophosphamide pulse in resistant cases of peripheral
100720 -            neuropathy secondary to SLE with lupus nephritis.
100721 -
100722 -
100723 -
100724 -
100725 -
100727 -  ..
100728 - Sunitinib Side Effects - Rare but serious...
100729 -
100730 -   10.  Rare but serious - Sunitinib
100731 -
100732 -        1.  Dysfunction of adrenal gland (which would cause lowered
100733 -            blood pressure and fatigue)
100735 -  ..
100736 - Millie has relatively low blood pressure; walking around pulse about
100737 - 55 at age 73, compared to others with most people in the 65 - 75
100738 - range.
100740 -  ..
100741 - Low pulse and blood pressure in Millie's case has been intuitively
100742 - attributed to good fitness from exercise, reported on 081014.
100743 - ref SDS 12 8G5M
100745 -  ..
100746 - If lower blood pressure is due to other causes then the sunitinib
100747 - treatment might be a factor to consider.
100749 -  ..
100750 - Sunitinib Side Effects - Rare but serious - Sunitinib continue
100751 -
100752 -        2.  Weakness of the heart muscle; irregular heartbeat
100754 -  ..
100755 - Patient history on heart issues is listed above. ref SDS 0 VV4L
100757 -  ..
100758 - Significance of this patient history is not clear in the record.
100760 -  ..
100761 - Sunitinib Side Effects - Rare but serious - Sunitinib continue
100762 -
100763 -        3.  Clots in blood vessels
100764 -        4.  Decreased thyroid gland function
100765 -        5.  Infection
100766 -        6.  Decreased blood flow to the brain
100767 -        7.  Bleeding requiring transfusion
100769 -         ..
100770 -        A subject on this study fell down and hit her head.  This
100771 -        caused bleeding around her brain (similar to a stroke) that was
100772 -        very serious.  It is unknown if being on this study contributed
100773 -        to her bleeding
100774 -
100775 -
100776 -
1008 -

SUBJECTS
Default Null Subject Account for Blank Record

1103 -
110401 -  ..
110402 - Side Effects Cyclophosphamide (Cytoxan)
110403 - Cyclophosphamide Side Effects (Cytoxan)
110404 - Cytoxan Side Effects (Cyclophosphamide)
110405 - Side Effects Cytoxan (Cyclophosphamide)
110406 -
110407 - Risks and side effects of cyclophosphamide (Cytoxan) include...
110409 -          ..
110410 -   11.  Cyclophosphamide side fects - Likely (10-50%)
110411 -        ref OF 1 PX6J
110412 -
110413 -        1.  Nausea
110414 -        2.  Infertility
110416 -          ..
110417 -   12.  Less Likely (1-10%)
110418 -        ref OF 1 NT5H
110419 -
110420 -        1.  Skin rash
110421 -        2.  Headache
110422 -        3.  Dizziness
110423 -        4.  Increased liver enzyme tests (may indicate liver damage)
110425 -         ..
110426 -   13.  Rare but serious
110427 -        ref OF 1 TU6G
110428 -
110429 -        1.  Development of another type of cancer
110430 -        2.  Steven-Johnson syndrome (can be a life-threatening
110431 -            skin disorder)
110432 -        3.  Interstitial pneumonitis (inflammation of the lung
110433 -            which can affect your breathing)
110435 -  ..
110436 - The CT test on 080718 reported findings of Interstitional Lung
110437 - disease, reviewed on 080723. ref SDS 9 TS4J  This disease is a side
110438 - effect of cetuximab treatments Millie has received for cancer the past
110439 - 2 years, reported on 070116. ref SDS 7 0256
110441 -  ..
110442 - On 080829 during a meeting at Kaiser the primary care physician used
110443 - the computer in the Examination room to open files for the CT test on
110444 - 080718; the doctor commented that Interstitional lung disease reported
110445 - on 080723, ref SDS 9 TS4J, appears very mild in the CT scan files,
110446 - and so not a significant side effect of cetuximab treatment for
110447 - Millie's cancer. ref SDS 10 RP4X
110449 -             ..
110450 -            [On 081112 CT test on 0811107 finds Interstitional disease
110451 -            at higher levels than shown by CT test on 080718.
110452 -            ref SDS 28 TS4J
110453 -
110454 -
110455 -
110456 -
110457 -
110458 -
1105 -

SUBJECTS
Default Null Subject Account for Blank Record

1203 -
120401 -  ..
120402 - Methotrexate Side Effects
120403 - Side Effects Methotrexate
120404 -
120405 -
120406 -   14.  Methotrexate side fects - Likely (10-50%)
120407 -        ref OF 1 XV6O
120408 -
120409 -        1.  Elevated liver function tests (?)
120410 -        2.  Nausea
120411 -        3.  Vomiting
120413 -         ..
120414 -   15.  Less Likely (1-10%)
120415 -        ref OF 1 ZS7Y
120416 -
120417 -        1.  Mouth sores
120418 -        2.  Decreased platelet count (may increase risk of bleeding)
120419 -        3.  Skin rash
120420 -        4.  Diarrhea
120421 -        5.  Hair loss or thinning
120422 -        6.  Decreased white blood cell counts (infection fighting cells;
120423 -            this problem may lead to increased risk of infection_
120424 -        7.  Decreased red blood cells (may make you feel tired or short of breath)
120425 -        8.  Dizziness
120426 -
120427 -
120428 -
1205 -

SUBJECTS
Default Null Subject Account for Blank Record

1303 -
130401 -  ..
130402 - Side Effects Radiation
130403 - Radiation Side Effects
130404 -
130405 -
130406 -   16.  Radiation (x-ray) risks:, ref OF 1 H76L
130407 -
130408 -        The amount of radiation you will be exposed to is relatively
130409 -        small.  Such doses of radiation may be potentially harmful, but
130410 -        the risks are so small that they are difficult to measure.  If
130411 -        you have already had many x-rays, you should discuss this was
130412 -        the researchers before agreeing to be in the study.
130413 -
130414 -
130415 -
1305 -

SUBJECTS
Default Null Subject Account for Blank Record

1403 -
140401 -  ..
140402 - Side Effects CT Tests
140403 - CT Tests Side Effects
140404 -
140405 -
140406 -   17.  CT scan risks:, ref OF 1 IU5T
140407 -
140408 -        1.  CT scans involve the risks of radiation (see above).
140409 -            ref SDS 0 D55G
140411 -             ..
140412 -        2.  Contrast material (iodine dye) presents slight risk of
140413 -            developing an allergic reaction, from mild (itching, rash)
140414 -            to severe (difficulty breathing, shock, or rarely, death).
140415 -            ref OF 1 A43N
140417 -             ..
140418 -        3.  The contrast material may also cause kidney problems,
140419 -            especially if you are dehydrated or have poor kidney
140420 -            function.  The study doctors will asked you about any
140421 -            allergies or related conditions before the procedure.  If
140422 -            you have any of these problems, you may not be allowed to
140423 -            have a CT scan or continue in the study. ref OF 1 V34G
140425 -             ..
140426 -        4.  Having a CT scan may mean some added discomfort for you.
140427 -            In particular, you may be bothered by feelings of
140428 -            claustrophobia when placed inside the CT scanner, or by
140429 -            lying in one position for a long time. ref OF 1 049T
140431 -             ..
140432 -        5.  If contrast material is used, you may feel discomfort when
140433 -            it is injected.  You may feel warm and flushed and get a
140434 -            metallic taste in your mouth. ref OF 1 A455
140436 -             ..
140437 -        6.  Rarely, the contrast material may cause nausea, vomiting or
140438 -            a headache. ref OF 1 665N
140439 -
140440 -
140441 -
140442 -
140443 -
140444 -
140445 -
140446 -
140447 -
140448 -
140450 -  ..
140451 - Treatment Protocol Sunitinib and Cyclophosphamide Taken Everyday
140452 - Methotrexate Taken 2 Days Consecutively Each Week of 3 Week Cycles
140453 -
140454 -
140455 - Sunitinib study consent document continues...
140457 -         ..
140458 -   18.  If you have not been having serious side effects from the
140459 -        sunitinib, you will start taking cyclophosphamide and
140460 -        methotrexate on this day.  The cyclophosphamide should be taken
140461 -        everyday.  The methotrexate is taken twice a day for 2 days in
140462 -        a row each week. ref OF 1 Z337
140464 -  ..
140465 - This indicates Millie will be taking 2 drugs everyday, sunitinib and
140466 - cyclophosphamide (Cytoxan), and will take methotrexate twice a day on
140467 - 2 consecutive days of each week.
140469 -  ..
140470 - Seems to conflict with the explanation above that cyclophosphamide and
140471 - methotrexate will be taken "daily," per above. ref SDS 0 YX6N
140473 -         ..
140474 -   19.  Get blood sample taken for measurement of CTCs and CECs at the
140475 -        start of the second and third cycle, then every other cycle.
140476 -        ref OF 1 1575
140478 -  ..
140479 - Aligns with study test objectives, per above. ref SDS 0 7R4J
140481 -  ..
140482 - Sunitinib study consent document continues...
140483 -
140484 -   20.  How long will I be in the study? ref OF 1 PRXW
140485 -
140486 -        You will be asked to take sunitinib, cyclophosphamide, and
140487 -        methotrexate every day until your physician believes the
140488 -        treatment may not be beneficial to you.  If you develop serious
140489 -        side effects or your breast cancer does not respond to the
140490 -        study treatment, you will stop the study treatment at that
140491 -        time. ref OF 1 PRXW
140493 -  ..
140494 - This part of the Consent docuement saying that
140495 -
140496 -            You will be asked to take sunitinib, cyclophosphamide, and
140497 -            methotrexate every day...
140498 -
140499 - ...appears conflicting with the protocol calling for methrotresate to
140500 - be taken only on 2 consecutive days each week while on study, per
140501 - above. ref SDS 0 Q14K
140502 -
140503 -
140504 -
140505 -
140506 -
140507 -
140508 -
140509 -
140510 -
140511 -
140512 -
140513 -
140514 -
1406 -