James K. Luce

Phase II evaluation of adriamycin in human neoplasia

Four hundred and seventy‐two patients with disseminated neoplasia were treated with two or more doses of adriamycin. The initial dose for “good risk” patients was 75 mg/m2 every 3 weeks, and for “poor risk” patients was 60 mg/m2 every 3 weeks. Objective remissions were seen in 118/472 patients, with best results noted in lymphomas (21/48), sarcomas (21/64), and carcinoma of the breast (16/50). Eighty‐nine per cent of remissions occurred within three courses. Hematopoietic toxic effects were seen in 73% of patients; nausea, vomiting, and/or stomatitis were observed in 43%. Changes in electrocardiograms were seen in 42/472 patients after cumulative doses of adriamycin ranging from 45 mg/m2 to 600+mg/m2. Irreversible congestive heart failure occurred in two patients after cumulative doses of 555 mg/m2 and 825 mg/m2, respectively. It is concluded that adriamycin is an active agent, most remissions occur promptly, and significant cardiotoxic reactions appear to be cumulative.

Phase II evaluation of bleomycin. A Southwest Oncology Group study

Bleomycin given intravenously (i.v.) or intramuscularly (i.m.) in twice‐weekly doses of 10 mg/m2 was evaluated for efficacy and toxicity in 382 patients. Responses were observed in 11/27 Hodgkins diseases, 10/30 lymphomas, 9/22 squamous cell cancers of ectodermal origin, 12/26 germinal cancers, and 3/8 renal adenocarcinomas. The i.m. route is less, likely to cause pulmonary toxicity or hypotension than the i.v. route. Advanced age and total doses exceeding 200 mg were Associated with a higher risk of lung toxicity. All responders had shown at least improvement upon receiving 200 mg; higher total doses should be used only in responding patients.

Treatment of cancer with weekly intravenous 5-fluorouracil

5‐Flourouracil is usually administered by rapid intravenous injection of 15 mg/kg daily for 3 to 5 days and 7.5 mg/kg every 2 or 3 days to toxicity, repeated monthly (antitumor response about 10–30%). Drug morbidity and mortality have been excessive. Modifications of this course have shown similar response rates but decreased toxicity and mortality. In the present study, 129 patients with disseminated cancer were treated weekly with 5‐fluorouracil, without a loading dose, by rapid intravenous injection, beginning at 15 mg/kg/wk for 1 month, increased to 20 mg/kg/wk (if necessary) to levels producing mild toxicity or an antitumor effect. Thirty patients had an objective remission (23.3% of the total 129, and 33% of the 91 adequately treated). Thirty‐eight patients showed no drug toxicity, 75 mild, 14 moderate, and two severe toxicity. There were no drug deaths. This course enabled patients to be treated safely on an ambulatory basis.

Chromosome abnormalities in human cancer. Report of a patient with chronic myelocytic leukemia and his nonleukemic monozygotic twin.

Chromosome studies were made on a 31‐year‐old man (H. vG.) with chronic myelocytic leukemia and his normal identical twin (L. vG.). Identical blood typing factors (17 tested) and similar fingerprint analyses warrant the conclusion that the twins are monozygous. Characteristic Ph1 chromosomes were found in blood and bone marrow from H.vG. before and after treatment with the colchicine analog, trimethyl colchicinic acid. During therapy the white blood count decreased from nearly 400,000/mm3 to less than 10,000/mm3. By contrast, analyses of blood and fresh bone marrow from L.vG. were consistently negative for the Ph1 chromosome. These results reinforce the postulate that the Ph1 chromosome is an acquired abnormality rather than a hereditary defect of the chromosome.

Fluorouracil and Palmar-Plantar Erythrodysesthesia

Excerpt To the Editor:Nine cases of palmar-plantar erythrodysesthesia associated with fluorouracil have been reported to Adria Laboratories since 1981. The reactions described included tenderness, ...

Advances in Chemotherapy

Chemotherapy is employed as primary treatment for patients with disseminated (stages IIIB and IV) Hodgkins disease. A number of agents or classes of agents are capable of producing an objective response in patients with Hodgkins disease. These include the alkylating agents, the periwinkle alkaloids, ie, vincristine sulfate (Oncovin), and vinblastine sulfate (Velban), procarbazine hydrochloride (Natulan [Great Britain]; Matulane, comparable US product), carmustine (BCNU) [1,3, bis (2-chloroethyl)-1-nitrosourea], adriamycin, and the corticosteroids. The time-honored approach has been to employ single agents in sequence starting usually with an alkylating agent and progressing to vinblastine sulfate. An agent was employed until it was clear that response was not going to occur, or until relapse occurred following response, at which point the next agent in sequence was introduced. Basic therapeutic and clinical studies in the leukemias indicate that the therapeutic index can be improved by manipulation of such variables as dose schedules, duration of treatment,