assorted questions

[Guest libby S]

Hi

My husband is in week 5 of an 8 week Tarceva trial. Since last week he has been running a low grade fever, fatigued, achy, headache, all the symptoms of the flu. Docs originally said it was a virus, but I think its gone on too long. We see them again tomorrow. My questions: what are the signs of brain mets. He is convinced his headaches are sign of that. Also, isn't someone here on an Iressa trial. How are you doing. The reason we have allowed this to go on for 10 days is we were out of town at my mothers funeral. I hope this is not a reaction to the Tarceva, since this doesn't offer a very good quality of life. Next question, does anyone have any info or feelings about low dose chemo. Is anyone on it, and how do you find a doctor to work with it. We are in Boston, and our oncologists at Dana Farber do not seem very interested in anything but standard chemo. I feel there is so much to learn in order to take responsibility for my husbands care. He is to exhausted and depressed to do it himself. I feel kind of overwhemed at the moment myself.

Libby S

[kimblanchard]

Hi Libby,

My husband has been on Iressa now for three weeks. He really seems to be feeling physically much better although we have no idea if it is affecting his cancer or not. The oncologist said it was best to wait 60 days for a CT scan.

My prayers are with you,

Peg

[john]

Have you tried to contact this person at dana-farber?

philip_hahnfeldt@dcfi.harvard.edu - see below

J Theor Biol 2003 Feb 21;220(4):545-54 Related Articles, Links

Minimizing long-term tumor burden: the logic for metronomic chemotherapeutic dosing and its antiangiogenic basis.

Hahnfeldt P, Folkman J, Hlatky L.

Dana-Farber Cancer Institute and Department of Radiation Oncology, Harvard Medical School, Boston, MA, 02115, USA. philip_hahnfeldt@dcfi.harvard.edu

The general utility of the maximum tolerated dose (MTD) paradigm, a strategy aimed at optimizing the chance of total tumor cell eradication, is here questioned. Evidence to date suggests that for many tumors the potential for eradication is in fact remote, with patients consistently demonstrating tumor cell presence subsequent to MTD treatments having eradicative intent. The failure to eradicate is attributed largely to the heterogeneous nature of the tumor. Heterogeneous cell populations demonstrate short-term refractoriness to up-front dose delivery, but "resensitize" as part of dose recovery, showing increased overall susceptibility to a given series of doses when delivered more evenly spaced. It is demonstrated: (1) that the minimization of total tumor burden, rather than complete eradication, may often be the more practical objective; and (2) that regularly spaced, "metronomic" dosing is the best way to achieve it. As a corollary, it is found that the more efficient ability of the tumor endothelial cells to resensitize following dosing predicts a targeting bias towards the endothelial compartment of a tumor when metronomic dosing is employed. This lends theoretical support to recent empirical studies showing that regularly spaced dosing schedules with no extended rest periods act more antiangiogenically, thereby delaying or avoiding the onset of acquired resistance.

[Guest Libby S]

John

My e mail to Philip Hahnfeldt was returned. Did I have the correct address. I will try and track him down. Thanks for the input.

[Guest Libby S]

Peg,

Thanks for the input. Glad Iressa seems to be working for your husband.

Libby

[john]

Libby,

Hopefully he will respond - and hopefully he can give your husband options

http://www.dfhcc.harvard.edu/member_det ... mberID=913

Philip J. Hahnfeldt, Ph.D.

Instructor

Department of Radiation Oncology, Harvard Medical School Printer-friendly version.

Contact Info

Dana-Farber Cancer Institute

44 Binney Street

Jimmy Fund Bldg, Rm 523

Boston, MA 02115

Phone: 617-632-3115

Fax: 617-632-4124

E-mail: philip_hahnfeldt@dfci.harvard.edu

Program Affiliation

Member in Angiogenesis, Invasion and Metastasis Program

DF/HCC Associations

No Associations are available for this member.

Research Abstract / Lab Focus

My current research focuses on the dynamical understanding of anti-angiogenic therapy for tumors from the standpoint of clinical implementation. In many respects, anti-angiogenic control is seen to recapitulate natural tissue-mass controls seen in human development. What we find specifically is that the classic 'Gompertz' tumor growth slowdown may be understood as an angiogenic process under negative feedback control from the tumor itself. I have published a quantitative description of how the tumor-vascular signaling interplay (involving angiogenic stimulators e.g. vascular endothelial growth factor, VEGF, balanced against natural angiogenic inhibitors e.g. endostatin) governs ultimate tumor growth [Cancer Res.59:4770-5, 1999].

In addition, because the target of anti-angiogenic therapy is not the tumor per se, but rather, its associated endothelium, I have undertaken to study the novel therapeutic issues and opportunities that arise. One category of these relates to the observation that endothelial targeting circumvents the classic drug resistance ultimately confronted under conventional chemotherapy. To study the implications of this observation for anti-angiogenic therapy, I am theoretically reexamining dosing protocols long held to be 'forbidden' by the standard "maximum tolerated dose" paradigm. What we stand to gain is a substantially expanded ability to tailor delivery protocols to further improve patient outcome.

Representative Citations

Tumor development under angiogenic signaling: a dynamical theory of tumor growth, treatment response, and postvascular dormancy.

Hahnfeldt P, Panigrahy D, Folkman J, Hlatky LR.

Cancer Res, Volume 59(19). October 1999:4770-5

PMID: 10519381

Polymer models for interphase chromosomes..

Hahnfeldt P, Hearst JE, Brenner DJ, Sachs RK, Hlatky LR.

PROCEEDINGS OF THE NATIONAL ACADEMY O..., Volume 90. Aug 1993:7854-8

PMID: 8356094