Biosynthetic Products for Cancer Chemotherapy: Volume 1 by George Pettit

By George Pettit

Cancer exacts an exceptionally harmful toll at the world's human populations. lately we now have often heard the expression "war on cancer," yet in comparison to the carnage inflicted through melanoma, our medical and clinical efforts, thus far, would appear extra like a minor skirmish. a few comprehension of the melanoma challenge may be got from a glance on the present and projected casualty record for the us. during this nation, approximately 700,000 new instances of melanoma could be clinically determined in 1976 and over 1 million recognized instances will stay handled. Over 400,000 of those sufferers will die from melanoma in our bicentennial 12 months. With the prevalence of melanoma within the usa expanding to 5.2% in 1975, in comparison to the 1.1 % each year cost skilled for many years, Dr. F. J. Rauscher, Jr.,338 Director of the nationwide melanoma Institute, has envisioned that greater than 10 million humans should be less than therapy for melanoma and approximately four million will expire from melanoma during this decade. At that expense, melanoma will seem in approximately of 3 households and the required remedy will rate a few $15-20 billion according to yr. hence except equipment for the remedy and keep watch over of melanoma are markedly stronger, approximately fifty three million american citizens now alive will finally be melanoma sufferers. Unfor­ tunately the main different types of human melanoma are nonetheless past healing care through surgical and radiological options and thanks to the paucity of at present to be had melanoma chemotherapeutic medications with healing potential.

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C ~ ~ 100-200 mg/day PO; 200-600 mg twice/wk Medroxyprogesterone acetate (34) (33) 1 Gm 1M twice/wk Hydroxyprogesterone caproate (32) F1uoxymesterone (31) 10-20 mg/day PO 3 mg/day PO Ethinyl estradiol (30) 100 mg 3x/wk, 1M 15 mg/day PO (1 mg in prostate cancer) Start 1-2 mg/kg/day hydrazine; PO; increase over 1 wk to 3 mg/kg; maintain for 3 wks then reduce to 2 mg/kg/day until toxicity Dromostanolone propionate (Drolban) (29) Hormones Diethylstilbestrol (DES) (27) Procarbazine hydrochloride (Methyl hydrazine; ibenzmethyzin; Matulane) None None None None None None Nausea and vomiting None Fluid retention, hypercalcemia, feminization, uterine bleeding; if during pregnancy, may cause vaginal carcinoma in offspring Fluid retention, masculinization, hypercalcemia Fluid retention, hypercalcemia, feminization, uterine bleeding Fluid retention, masculinization, cholestatic jaundice None Bone marrow depression eNS depression (Table 1 contined) Endometrial carcinoma, renal-cell, breast cancer Endometrial carcinoma Breast carcinoma Breast and prostate carcinomas Breast carcinoma Breast and prostate carcinomas Hodgkin's disease, lymphoma, bronchogenic carcinoma ~ ::to ~ i...

Also, eliminating the requirement for cyclophosphamide should be very constructive for the future. Recently each of five patients receiving large oral doses (114-295 g over 3-5 years) of cyclophosphamide developed urinary-bladder tumors fatal to four of the five. 8 These patients were being given long-term treatment with very large amounts of cyclophosphamide for various other types of cancer. The current prospects for combination chemotherapy have been set forth by De Vita. 8! His statement-"now that the chemotherapeutic tools are sharpened, their use in combinations with other modalities in the previously unfamiliar setting of the patient with early stages of the disease promises to lead to an even more exciting chapter in clinical cancer research in the next decade"-refiects the very rewarding area of cancer treatment upon which we are about to embark.

As pointed out by Zubrod,442 a most telling illustration of this effect is with Burkitt's lymphoma, in which nearly 100% of the neoplastic cells undergo division and a single dose of cytoxan (cyclophosphamide) cures 60% of the patients. For those neoplastic diseases with a smaller growth fraction, a combination of drugs acting through different mechanisms and at different points in the cell cycle is needed to effect complete cell kill. With old tumors such as colon and lung with growth fractions less than 5%, the rate of DNA synthesis is minimal, and these neoplasms are not very sensitive to currently available anticancer drugs.

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