CONTACTS 

SUBJECTS
Cancer Cells Detected in Biopsy of Lumps in Neck Taken on 040303 by D
Laio, Been Doctor Called and Reported Cancer Cells Detected in Biopsy
Trial on New Cancer Treatment Double Blind Test Alternative Approach

0905 -
0905 -    ..
0906 - Summary/Objective
0907 -
090701 - Follow up ref SDS 4 0000. ref SDS 3 0000.
090702 -
090703 - Millie called this afternoon.  She reported that Doctor Laio just
090704 - called her and reported results of the biopsy on neck tissue from the
090705 - meeting at Kaiser on 040303, ref SDS 4 Y171, which was ordered by the
090706 - primary care physician on 040227 because lumps in the neck did not
090707 - respond to treatment, ref SDS 3 886G, after Millie complained of stiff
090708 - neck during the meeting on 040211. ref SDS 2 WP7L
090710 -  ..
090711 - The pathology report shows cancerous cells were found.
090712 -
090713 -        [On 040311 Millie's letter to her boss at Nixon Peabody, Gordon
090714 -        Poole. ref SDS 5 LN95
090715 -
090716 -        [On 040318 the doctor diagnoses metastatic cancer due to
090717 -        recurrence. ref SDS 6 8R6M
090719 -         ..
090720 -        [On 040517 Millie diagnosed with inflammatory breast cancer,
090721 -        ref SDS 7 7D6F, research indicates that swelled lymph nodes in
090722 -        the neck above the collar bone are symptoms of IBC. ref SDS 7
090723 -        M67I
090725 -         ..
090726 -        [On 041104 swelled lymph nodes in neck no longer identified by
090727 -        CT testing, nor by clinical examination, after 9 months of
090728 -        treatents. ref SDS 8 8R6M
090730 -         ..
090731 -        [On 051121 patient currently has no evidence of disease based
090732 -        on estensive testing with biopsy, PET, CA 1503; prognosis is
090733 -        for future relapse due to diagnosis of metastatic cancer, and
090734 -        therefore mastectomy surgery on 051021 was palliation for
090735 -        furture relapse. ref SDS 10 LH7M
090737 -  ..
090738 - During a meeting on 040303 Doctor Laio advised that swelled lymph
090739 - nodes in the supraclavicular region of the neck will be removed by
090740 - surgery, whether or not diagnosed to be infected with cancer, and that
090741 - this operation would be performed within the next two (2) weeks.
090742 - ref SDS 4 Y193  Millie explained during the call today that Doctor
090743 - Laio related to her having discussed results of the biopsy with the
090744 - primary care physician in Oncology last Friday on 040305, and, for
090745 - some reason a decision was made not to perform surgery to remove even
090746 - lymph nodes in the neck found to be cancerous, which previously was
090747 - described as standard practice.  Doctor Laio expects Millie will be
090748 - treated with chemotherapy again.  This raises the question...
090749 -
090750 -    Why not remove the cancerous lymph nodes in the neck with surgery,
090751 -    as was done for the original tumor in the breast and the lymph
090752 -    nodes under the arm on 020312? ref SDS 1 Q78M
090753 -
090754 -        [On 040318 the doctor explains that Doctor Laio's findings of
090755 -        cancer in lymph nodes show metastatic cancer which is more
090756 -        conducive to treatment with chemotherapy, rather than with
090757 -        surery. ref SDS 6 HC6K
090759 -         ..
090760 -        [On 040517 "minutes" of Tumor Board indicate radiation and
090761 -        surgery to remove lymph nodes in the neck may be performed, if
090762 -        chemotherapy is not successful. ref SDS 7 F77M
090764 -         ..
090765 -        [On 040517 Millie diagnosed with inflammatory breast cancer,
090766 -        ref SDS 7 7D6F, research indicates that swelled lymph nodes in
090767 -        the neck above the collar bone are symptoms of IBC. ref SDS 7
090768 -        M67I
090770 -         ..
090771 -        [On 041104 swelled lymph nodes in neck no longer identified by
090772 -        CT testing, nor by clinical examination, after 9 months of
090773 -        treatment. ref SDS 8 8R6M
090775 -         ..
090776 -        [On 050826 referral surgeon in Kaiser's Oakland office
090777 -        recommends removing additional lymph nodes in left auxillary,
090778 -        which at the present time are not identified as cancerous; no
090779 -        discussion of Doctor Laio's recommendation to remove swelled
090780 -        lymph nodes in supraclavicular region. ref SDS 9 IZ8L
090781 -
090782 -
090784 -  ..
0908 -
0909 -
0910 - 1713
0911 -
091101 - After work, Millie got a phone message at home from the primary care
091102 - physician in Oncology at Kaiser.
091104 -  ..
091105 - The primary care physician has talked to Doctor Laio, and learned that
091106 - the biopsy on 040303, ref SDS 4 Y171, and which was ordered by the
091107 - primary care physician on 040227, ref SDS 3 886G, has now diagnosed
091108 - cancer relapse.
091110 -  ..
091111 - The doctor further reported conversations with Rosalie, the Protocol
091112 - Nurse who manages clinical drug trials for treating cancer patients.
091113 - Good news, Millie qualifies to participate in a drug trial for Taxol
091114 - combined with a new chemotherapy agent called "Avastin." The doctor
091115 - said that strong results in trials using Avastin for colon cancer, and
091116 - favorable phase 1 trials for breast cancer, suggest referral to the
091117 - next phase of clinical trial is the best course of treatment for
091118 - Millie.
091120 -  ..
091121 - The doctor wants to meet next week on 040318 to explain details of the
091122 - trial protocol.
091123 -
091124 -     [On 040318 doctor proposes treatment with Avastin trial,
091125 -     ref SDS 6 PU6M, introduces Protocol Nurse who explains details of
091126 -     the trial. ref SDS 6 BK8M
091128 -  ..
091129 - Millie has heard about the new treatment.
091131 -         ..
091132 -        Research on the Internet indicates clinical trials are underway
091133 -        for bevacizumab (Avastin) and Taxol to treat breast cancer.
091134 -        ref SDS 0 MT5U
091136 -  ..
091137 - The primary care physician indicated in his message that the trial
091138 - would be a double blind protocol, so that Millie could be among the
091139 - 50% of participants who do not receive the trial treatment.
091140 -
091141 -        Research indicates that Avastin is a complementary treatment to
091142 -        normal chemotherapy. ref SDS 0 TQ33  So, there is not an issue
091143 -        of getting no treatment.  Millie will get the maximum treatment
091144 -        she got previously, but if she happens to fall in the 50% of
091145 -        the patients who get Avastin, rather than a placebo, then she
091146 -        will get additional treatment.
091148 -         ..
091149 -        Additionally, comments from friends and family indicate that of
091150 -        results of the tests are favorable, then the 50% of the placebo
091151 -        patients are given the opportunity to receive the additional
091152 -        treatment as well.
091154 -  ..
091155 - Review on the Internet shows....
091156 -
091157 -            http://www.gene.com/gene/products/information/oncology/avastin/
091158 -
091159 -         Avastin is the first U.S. Food and Drug Administration (FDA)
091160 -         approved therapy designed to inhibit angiogenesis, the process
091161 -         by which new blood vessels develop and carry vital nutrients
091162 -         to a tumor.
091164 -          ..
091165 -         Status
091167 -          ..
091168 -         The FDA approved Avastin in February 2004. Avastin is approved
091169 -         for use in combination with intravenous 5-Fluorouracil-based
091170 -         chemotherapy as a treatment for patients with first-line - or
091171 -         previously untreated - metastatic cancer of the colon or
091172 -         rectum.
091174 -          ..
091175 -         The Avastin FDA approval is based on data from a large,
091176 -         placebo controlled, randomized study demonstrating
091177 -         prolongation in the median survival of patients treated with
091178 -         Avastin plus the IFL(5-FU/Leucovorin/CPT-11) chemotherapy
091179 -         regimen by approximately five months, compared to patients
091180 -         treated with the IFL chemotherapy regimen alone (20.3 months
091181 -         versus 15.6 months). This is one of the largest improvements
091182 -         in survival ever reported in a randomized, Phase III study of
091183 -         patients with metastatic colorectal cancer
091185 -          ..
091186 -         Proposed Mechanism of Action
091188 -          ..
091189 -         Avastin is designed to inhibit Vascular Endothelial Growth
091190 -         Factor (VEGF), a protein that plays an important role in tumor
091191 -         angiogenesis and maintenance of existing tumor vessels.  By
091192 -         inhibiting VEGF, Avastin is designed to interfere with the
091193 -         blood supply to tumors, a process that is critical to tumor
091194 -         growth and metastasis
091196 -          ..
091197 -         Clinical Trials
091199 -          ..
091200 -         Based on preclinical and clinical studies showing that VEGF
091201 -         plays a broad role in a range of cancers, Genentech is
091202 -         pursuing a late-stage clinical development program with
091203 -         Avastin evaluating its potential use in metastatic colorectal,
091204 -         renal cell (kidney), breast and non-small cell lung cancers.
091205 -         Avastin is also being evaluated in earlier stage trials as a
091206 -         potential therapy in prostate, ovarian, melanoma and several
091207 -         types of solid tumor cancers and hematologic malignancies.
091209 -  ..
091210 - Application to breast cancer is confirmed by Genentech publications
091211 - per below. ref SDS 0 AX8L
091213 -  ..
091214 - Genentech, the manufacturere, says...
091215 -
091216 -            http://www.gene.com/gene/pipeline/status/oncology/avastin/index.jsp
091217 -
091218 -         March 2004
091220 -          ..
091221 -         Description
091223 -          ..
091224 -         Avastin is a recombinant humanized antibody to Vascular
091225 -         Endothelial Growth Factor (VEGF). Avastin is designed to bind
091226 -         to and inhibit VEGF, a protein that plays a critical role in
091227 -         tumor angiogenesis (the formation of new blood vessels to the
091228 -         tumor).
091230 -          ..
091231 -         Development Status
091233 -          ..
091234 -         Genentech is pursuing a broad late-stage clinical development
091235 -         program with Avastin, evaluating its potential use in multiple
091236 -         tumor types. Phase III clinical trials in renal cell
091237 -         carcinoma, advanced non-small cell lung cancer, and metastatic
091238 -         breast cancer are being conducted. We are currently planning
091239 -         for Phase III clinical trials in adjuvant colorectal cancer
091240 -         and metastatic & locally advanced pancreatic cancer.  This
091241 -         product is being developed in collaboration with Hoffmann-La
091242 -         Roche.
091244 -          ..
091245 -         Additional Information on Clinical Trials
091247 -          ..
091248 -         U.S. callers: 888-662-6728 Email:
091249 -         genentechclinicaltrials@askatp.com
091251 -          ..
091252 -         National Institutes of Health Website
091253 -         http://www.clinicaltrials.gov/
091255 -          ..
091256 -         For international inquiries, contact our international
091257 -         partner, Roche, at +41-61-688-1111 or online at
091258 -         http://www.roche.com/home.html
091259 -
091261 -  ..
091262 - Forbes has an article...
091263 -
091264 -         Pharmaceuticals
091265 -         Genentech's Avastin Awaits FDA Approval
091266 -         Matthew Herper, mherper@forbes.net
091267 -         09.29.03, 11:00 AM ET
091269 -          ..
091270 -         NEW YORK - Genentech has finished filing its application with
091271 -         the U.S. Food and Drug Administration to sell Avastin as a
091272 -         treatment for colorectal cancer. It is the first cancer drug
091273 -         to work by starving the flow of blood to tumors, a process
091274 -         called anti-angiogenesis.
091276 -          ..
091277 -         Avastin does this by inhibiting a protein called the vascular
091278 -         endothelial growth factor. Avastin adds to the number of drugs
091279 -         developed by directly targeting a specific protein; others
091280 -         include Novartis' (nyse: NVS - news - people ) Gleevec,
091281 -         AstraZeneca's (nyse: AZN - news - people ) Iressa and
091282 -         Millennium's (nasdaq: MLNM - news - people ) Velcade. In May,
091283 -         South San Francisco-based Genentech (nyse: DNA - news - people
091284 -         ) said that Avastin extended survival in colon cancer
091285 -         patients. Since then, the company's share price has almost
091286 -         doubled.
091288 -          ..
091289 -         Genentech also announced that results from a second study of
091290 -         Avastin in colon cancer are now expected in the fourth quarter
091291 -         of 2003. Jason Kantor, an analyst at W.R. Hambrecht, says that
091292 -         he suspects the FDA may want to see the data from this new
091293 -         trial before it approves the drug. He also believes this
091294 -         second trial will work out well. He owns shares of Genentech,
091295 -         but his company does not do banking for the biotech.  In
091296 -         morning trading, shares of Genentech were off 39 cents to $80.
091297 -
091298 -
091300 -  ..
091301 - US Food and Drug Administration says...
091302 -
091303 -            http://www.fda.gov/cder/drug/infopage/avastin/avastinQ&A.htm
091304 -
091305 -     Date created: February 26, 2004
091306 -
091307 -     Questions and Answers on Avastin (bevacizumab)
091308 -
091309 -     1.  What is Avastin (Bevacizumab), and how does it work?
091310 -         ref SDS 0 HU9M
091312 -          ..
091313 -     2.  What are monoclonal antibodies?
091315 -          ..
091316 -     3.  What are angiogenesis inhibitors?
091318 -          ..
091319 -     4.  What is Avastin used to treat?
091321 -          ..
091322 -     5.  Is Avastin a cure for metastatic colorectal cancer?
091324 -          ..
091325 -     6.  How is Avastin given?
091327 -          ..
091328 -     7.  What are the possible side effects of Avastin?
091330 -          ..
091331 -     8.  Where can I find more information on Avastin and colorectal
091332 -         cancer?
091333 -
091334 -
091336 -          ..
091337 -     1.  What is Avastin (bevacizumab), and how does it work?
091338 -
091339 -         Avastin is a monoclonal antibody that works by attaching to
091340 -         and inhibiting the action of vascular endothelial growth factor
091341 -         (VEGF) in laboratory experiments. VEGF is a substance that
091342 -         binds to certain cells to stimulate new blood vessel formation.
091343 -         When VEGF is bound to Avastin, it cannot stimulate the
091344 -         formation and growth of new blood vessels (angiogenesis).
091345 -         Avastin enhances the effects of chemotherapy, but does not
091346 -         appear to be effective when given alone in patients with
091347 -         colorectal cancer.
091349 -          ..
091350 -     2.  What are monoclonal antibodies?
091351 -
091352 -         Antibodies are substances produced by the immune system in
091353 -         response to foreign substances such as bacteria, viruses or
091354 -         toxins).  They are the body's natural defense mechanism
091355 -         against infection, as they help to destroy these foreign
091356 -         substances. Monoclonal antibodies are antibodies produced in a
091357 -         laboratory to target a very specific part of the foreign
091358 -         substance (antigen).  Because of their precision, it is
091359 -         expected that they may be more effective than standard
091360 -         chemotherapy with fewer side effects.
091362 -          ..
091363 -     3.  What are angiogenesis inhibitors?
091364 -
091365 -         Angiogenesis inhibitors prevent the formation of new blood
091366 -         vessels, including those that surround and supply cancer
091367 -         cells, with the oxygen and nutrients they need to survive and
091368 -         grow.  By taking away the blood supply, angiogenesis
091369 -         inhibitors may reduce tumor cell growth and cause cancerous
091370 -         tumors to grow more slowly or to become smaller.
091372 -          ..
091373 -     4.  What is Avastin used to treat?
091374 -
091375 -         Avastin is used to treat cancer of the colon or rectum that
091376 -         has spread to other parts of the body. Avastin is given along
091377 -         with the chemotherapy combination known as IFL. IFL consists
091378 -         of irinotecan, 5-fluorouracil (5-FU), and leucovorin
091380 -          ..
091381 -     5.  Is Avastin a cure for metastatic colorectal cancer?
091382 -
091383 -         No, Avastin will not cure metastatic colorectal cancer.  In
091384 -         clinical trials there was longer survival and tumor control in
091385 -         patients who received the combination of IFL plus Avastin than
091386 -         among those who received IFL without Avastin.  Overall,
091387 -         patients given Avastin survived about five months longer.  In
091388 -         addition, the average time before tumors restarted growing or
091389 -         new tumors appeared was four months longer than patients who
091390 -         did not receive Avastin
091391 -
091393 -          ..
091394 -     6.  How is Avastin given?
091395 -
091396 -         Avastin is given intravenously (into a vein) every 14 days.
091398 -          ..
091399 -     7.  What are the possible side effects of Avastin?
091400 -
091401 -         Serious side effects include:
091402 -
091403 -          •  holes in the colon requiring surgery to repair
091404 -             (gastrointestinal perforation)
091406 -              ..
091407 -          •  impaired wound healing
091409 -              ..
091410 -          •  bleeding leading to disability (stroke) or death
091411 -             (especially in lung cancer patients)
091413 -              ..
091414 -          •  heart failure in certain patients (those given or
091415 -             receiving other anti-cancer treatments that may injure the
091416 -             heart muscle) kidney damage
091417 -
091419 -          ..
091420 -         Other more common side effects of Avastin treatment are:
091421 -
091422 -          •  high blood pressure
091423 -
091424 -          •  tiredness/weakness
091425 -
091426 -          •  clot in the vein (thrombophlebitis)
091428 -              ..
091429 -          •  diarrhea
091431 -              ..
091432 -          •  decreased white blood cells
091434 -              ..
091435 -          •  headache
091437 -              ..
091438 -          •  loss of appetite
091440 -              ..
091441 -          •  mouth sores
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