B. S. Yap

Chemotherapy for postmastectomy lymphangiosarcoma

Twenty‐two patients with postmastectomy lymphangiosarcoma have been seen at M. D. Anderson Hospital during the past 20 years. Of these, 13 received chemotherapy, either regionally, systemically, or both. Six patients were treated with regional chemotherapy using either methotrexate alone, a combination of melphalan, nitrogen mustard, and actinomycin D, or a combination of melphalan with nitrogen mustard or actinomycin D; 3 achieved a partial or complete response. Eleven patients received 19 trials of systemic chemotherapy; one complete and seven partial responses were observed, giving an overall response rate of 42% (8/19). Responses occurred with 5‐fluorouracil, methotrexate, a combination of vincristine, actinomycin D, and cyclophosphamide, and a combination of Adriamycin and dacarbazine with or without vincristine. The median survival time of the six patients who responded to at least one chemotherapeutic trial was 26.5 months compared with four months for the five patients who failed to respond. These data indicate that chemotherapy may play a significant role in the treatment of patients with this rare but distinctive tumor. Cancer 47:853–856, 1981.

Phase II evaluation of PALA in patients with refractory metastatic sarcomas

THE EFFICACY OF PALA WAS EVALUATED IN 22 patients with metastatic soft tissue and bone sarcomas. The 20 evaluable patients had received a median of three prior chemotherapeutic regimens, including an adriamycin combination, to which eight had shown response. PALA was administered at 2-week intervals. Sixteen patients received 6 g/m2 over 1 hour intravenously as their initial dose, while six patients received 5 g/m2. The major side effects were skin rash, stomatitis, diarrhea, nausea, and vomiting. Significant myelosuppression was not seen. Two patients had stabilization of disease for periods of 10 and 13 weeks. At the dose and schedule used in this trial, PALA was not effective against advanced adult sarcoma.

Clinical Pharmacology of Netilmicin

Pharmacological studies of netilmicin were conducted in 30 cancer patients. After intravenous administration of 50 mg of netilmicin or gentamicin per m2 over a 1-h period in 10 patients, the mean peak serum concentrations occurred at the end of the infusion and were 7.6 and 7.3 μg/ml, respectively. At 6 h, the mean serum concentrations of both drugs was 1.1 μg/ml. After intramuscular injection of 50 mg of netilmicin per m2 to each of the same 10 patients, the mean peak serum concentration was 5.5 μg/ml and occurred at 1 h, and, at 6 h, the mean serum concentration was 1.4 μg/ml. The mean proportion of netilmicin excreted in urine during 6 h after intramuscular injection was 55%, and after intravenous injection it was 40.9%. Results were similar with gentamicin sulfate. After administering 60 mg of netilmicin per m2 intravenously over 30 min every 6 h in 9 patients, the mean peak serum concentration (7.9 μg/ml) occurred at the end of the infusion. The concentration gradually decreased to below 2.0 μg/ml after 4 h. Continuous infusion of 60 mg of netilmicin per m2 every 6 h after a 60-mg/m2 loading dose in 11 patients produced levels consistently above 2.9 μg/ml, during the initial 6-h infusion, and levels above 2.0 μg/ml for at least 1 week.

Infusion Chemotherapy for Soft Tissue Sarcomas

Adriamycin has formed the backbone of sarcoma chemotherapy since its introduction into clinical practice. The pioneering studies in this field by the late Dr. Jeffrey Gottlieb demonstrated modest but definite improvement in response rate, remission duration and survival when Adriamycin was combined with DIC and slight further improvement with the addition of cyclophosphamide [1–5]. Other drugs have been relatively ineffective, and the CyVADIC regimen, introduced in 1973, remains the standard of sarcoma chemotherapy [3–5]. Review of the data from our own institution from 1973–1977 revealed an 18% complete remission rate and a 49% complete plus partial remission rate in 169 patients treated with the CyVADIC regimen [6]. Patients who achieve complete remission have the potential for long term survival, and this is true whether the complete remission is a response to chemotherapy alone or to chemotherapy and surgery [7]. Unfortunately, maintenance chemotherapy without adriamycin has been ineffective, and the majority of patients relapse after adriamycin has been discontinued to prevent cardiac toxicity.

A randomized study of continuous infusion vindesine versus vinblastine in adults with refractory metastatic sarcomas

A randomized study was conducted in 33 adult patients with refractory metastatic sarcomas to compare the therapeutic efficacy of continuous vindesine versus continuous vinblastine. Of 30 evaluable patients, 15 patients received vindesine as a continuous 5-day infusion at 1.2 mg/m2 repeated every 3 weeks, and 15 patients received vinblastine at 1.5 mg/m2/day every 3 weeks. Ten patients had stable disease, while 20 patients showed progressive disease. No objective responses were observed. There was adequate myelosuppression and both drugs were well tolerated with few catheter-related problems. It does not appear that vindesine or vinblastine, given by continuous 5-day infusion, is active in the treatment of metastatic sarcomas in adults.

Clinical pharmacology of bruceantin by radioimmunoassay.

SummaryDuring the phase I clinical trial of a new antitumor agent, bruceantin, the pharmacology was studied in 18 cancer patients. The drug was infused intravenously (IV) for 3 h at doses ranging from 1 to 3.6 mg/m2 per day for 5 days. The plasma drug disappearance curves were biphasic, with a fast initial half-life of less than 15 min. The second half-life (t1/2β) varied from 0.7 to 38 h among different patients and was not dose-related. The difference between the t1/2β on day 1 and that on day 5 was not significant. In patients with normal liver function, the mean plasma concentration at the end of infusion was 22 ng/ml, and the value of the area under the concentration x time curve (AUC) was 111 (ng/ml)h. In contrast, in patients with abnormal liver function the corresponding values were 115 ng/ml and 830 (ng/ml)h, respectively. In addition, these patients had a slower elimination half-life of 10.9 h and a decreased total clearance of 157. ml/min/m2, as compared with 2.6 h and 671 ml/min/m2, respectively, for the normal group. All these differences were statistically significant.Patients with abnormal liver function developed more severe toxicity, including fever, severe nausea, vomiting, and hypotension. Two patients with severe hepatic dysfunction received a reduced dose and developed no toxicity. These results demonstrated the importance of the effects of liver dysfunction on drug disposition and showed that the dosage should be reduced in patients with hepatic dysfunction.

A phase II trial of PCNU in patients with malignant melanoma and central nervous system metastases

TWELVE PATIENTS WITH MALIGNANT MELANOMA metastatic to the central nervous system (CNS) were treated with PCNU. All patients had prior chemotherapy and/or radiation therapy and had progressive brain metastases, documented by computerized tomography. PCNU was given as a single intravenous infusion of 90–110 mg/m2 every 6–8 weeks. There was one partial response and four patients had stable disease. Although no episodes of sepsis or bleeding occurred, seven of 17 courses led to significant granulocytopenia or thrombocytopenia. Non-hematopoietic toxicities were mild. These results indicate that systemic PCNU is unlikely to be more effective than other currently used chemotherapy in patients with malignant melanoma and CNS metastases.