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Low Dose (metronomic) Chemotherapy

7/11/01 The concept of continuous low-dose ("metronomic") anti-angiogenic chemotherapy This combination strategy can be employed successfully against tumors previously selected in vitro or in vivo for extremely high levels of acquired resistance to the cytotoxic drug used for the metronomic therapy, and lends itself to immediate clinical trial evaluation using drugs such as Celebrex as a putative angiogenesis inhibitor
6/17/02 Michael Retsky Story From the book "Dr. Folkman's War". Michael Retsky was a stage III colon cancer patient who apparently cured himself using low dose chemotherapy alone (no surgery)
6/17/02 LEF Cancer Chemotherapy Protocol Ideas about combining Low Dose Chemo with other alternative meds
7/11/01 Conference Report Cell Death: New Targets Come to the Fore 2nd International Conference on Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention June 2-6, 2001 low dose metronomic chemotherapy + COX 2 inhibitors
7/12/2001 Cancer-drug treatment: Less might prove more April 2, 2000 Two studies showing that small but continuous doses of cancer drugs can permanently eradicate tumors in mice may offer new hope of effective treatment for uncounted thousands of patients whose tumors fail to shrink even with massive, highly toxic doses of those same drugs.
7/11/01 Metronomic Dosing: Shrinking Cancer Tumors Sybil Brabner
7/11/01 Low Dose Metronomic Chemotherapy Exploiting COX-2 Inhibitors As Anti-Angiogenic Drugs for Combination Metronomic Chemotherapy
9/20/01 Continuous Low-Dose Capecitabine Produces Significant Biochemical Responses in Patients with Progressive Gastroenteropancreatic (GEP) Neoplasms ASCO 2001 We hypothesized that low-dose continuous capecitabine, an oral 5-FU prodrug, would be well tolerated and may decrease biochemical markers in patients with GEP neoplasms. To test this hypothesis, 42 patients (pts) with progressive metastatic GEP neoplasms, including carcinoid and pancreatic islet cell carcinomas, received capecitabine (1,000-2,500 mg/d) for 60 days Seven pts (41.2%) experienced an objective partial biochemical response (50% or greater reduction) and 7 pts had stable disease (less than 50% reduction)
7/11/01 A Cure for Cancer? January 12, 2001 Canadian Doctor Robert Kerbel, of Toronto's Sunnybrook and Women's Hospital, had developed a technique which had been dubbed "metronomic dosing". It had shown spectacular results in tests conducted in laboratory conditions on mice The procedure, which is actually a low dose, continuous regimen of chemotherapy coupled with the drug Celebrex (an anti-inflammatory), removed tumours in 85 percent of the trials
7/12/01 Low Dose Chemotherapy Cancerprotocol.com
7/12/01 Giving Smaller Doses of Chemotherapy More Frequently May Attack Tumor Blood Supply Radiation oncologists at Thomas Jefferson University Hospital are rethinking how to give chemotherapy, taking advantage of its unique properties. They are giving chemotherapy more frequently than usual and in tinier doses, targeting the process by which a new blood supply is created feeding tumor growth, called angiogenesis
5/17/02 Herb extract appears to trigger 'suicide' in cancer cells Stanford Report, January 16, 2002 The Tripterygium wilfordii vine has played a role in traditional Chinese medicine for thousands of years. Stanford cancer researchers believe it may enhance chemotherapy's positive effects. Palo Alto-based Pharmagenesis, where Rosen acts as a consultant, found similar results with a water-soluble form of triptolide. They had tested the compound in combination with low-dose chemotherapy on mice carrying tumors transplanted from humans.

NOTE: see http://www.discover.com/nov_99/letters.html "We received many inquiries--and several warnings--about thunder god vine. This herb can have a strong toxic effect, has not been tested in humans, and is not available in the United States"
5/17/02 Dr. Folkman's War on Cancer (Audio Files)
5/17/02 Dr Folkman's War: Angiogenesis and the Struggle to Defeat Cancer by Robert Cooke, C. Everett Koop (BOOK - Amazon.com)
5/17/02 The discovery of angiogenesis inhibitors: A new class of drugs by Judah Folkman, Children's Hospital, Harvard Medical School MBL Lectures
5/17/02 NOVA Online - Cancer Warrior
10/17/01 [A case of intra-peritoneal recurrence of colon carcinoma that responded remarkably to combined therapy of low-dose leucovorin and 5-fluorouracil]. Gan To Kagaku Ryoho 2001 Sep;28(9):1291-4 We treated a patient with intra-peritoneal recurrent tumor from colon cancer who responded completely to chemotherapy of combined low-dose Leucovorin (LV) and 5-fluorouracil (5-FU).
5/17/02 Proposal for a new model of breast cancer metastatic development. Ann Oncol 1997 Nov;8(11):1075-80 Demicheli R, Retsky MW, Swartzendruber DE, Bonadonna G CONCLUSIONS: A new general outline of metastatic development of breast cancer incorporating tumor dormancy in specific micrometastatic phases, stochastic transitions between them, and start signals from surgery for micrometastatic growth was designed. The proposed model suggests new views concerning scheduling of current chemotherapy, new treatment approaches aimed at keeping micrometastases in a dormant state for the patient's entire life, and the careful reappraisal of the timing of surgery within the multimodal treatment of operable breast cancer
5/17/02 Is Gompertzian or exponential kinetics a valid description of individual human cancer growth? Med Hypotheses 1990 Oct;33(2):95-106 PMID: 2259298 Retsky MW, Swartzendruber DE, Wardwell RH, Bame PD. It is generally accepted that human cancers grow in an exponential or Gompertzian manner. This assumption is based on analysis of the growth of transplantable animal tumors and on averages of tumor growth in human populations. A computer model of breast cancer in individual patients has raised some doubts about this assumption. The computer model predicts an irregular pattern of tumor growth that incorporates plateaus or dormant periods separated by Gompertzian growth spurts. Since growth patterns involving plateaus are not predicted by conventionally accepted exponential or Gompertzian kinetics, sufficient documentation of their existence may be regarded as some evidence that the computer model is correct. The literature has been surveyed to identify growth patterns specifically predicted by the model. The literature contains clinical evidence from individual patients of this growth pattern in primary breast, large intestine and rectum, and pulmonary cancers and metastatic pulmonary cancer. Much data, including the only breast data, are not consistent with exponential or Gompertzian kinetics but are explainable by irregular growth kinetics. Exponential growth is valid for some tumors and for short times, but there are many papers citing significant deviations from that growth. Exponential growth may accurately describe averages of human tumor growth and growth of multipassaged experimental tumors, but it is not valid for all individual tumors
5/17/02 Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 2000 Apr 1;60(7):1878-86 Browder T, Butterfield CE, Kraling BM, Shi B, Marshall B, O'Reilly MS, Folkman J. PMID: 10766175 Thus, by using a dosing schedule of cyclophosphamide that provided more sustained apoptosis of endothelial cells within the vascular bed of a tumor, we show that a chemotherapeutic agent can more effectively control tumor growth in mice, regardless of whether the tumor cells are drug resistant.
5/17/02 Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997 Nov 27;390(6658):404-7 PMID: 9389480 An unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy.
5/17/02 From Cancer Researcher to Patient: A Profile of Michael Retsky For 2 1/2 years, Michael followed a protocol of chronomodulated 5-FU, or 5- FU infusion programmed for certain hours each day. The infusion lasted for several hours at night, running in through a portable infusion pump. He continued to work every day, only experiencing minor side effects from the chemotherapy
5/17/02 CANCER GROWTH Implications for Medicine & Malpractice by Michael Retsky, PhD
6/13/02 Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice -FULL TEXT- J Clin Invest, April 2000, Volume 105, Number 8, 1045-1047
5/17/02 Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity -FULL TEXT- J Clin Invest, Vol. 105, Issue 8, R15-R24, April 15, 2000

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