Robert M. OʼBryan

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.

Because patients treated with 60-90 mg/m2 every three to four weeks reach cardiotoxic doses of 550 mg/m2 within 36 weeks, prolonged treatment with Adriamycin is limited. The purpose of this study was to determine whether lower doses could be given over longer periods without loss of efficacy. Good risk patients treated with 75, 60, or 45 mg/m2 had remission rates of 25, 27, and 19%; poor risk patients treated with 50 and 25 mg/m2 had remission rates of 16 and 12% respectively. Although a dose response was identified, there were no statistically significant differences in remission rates, durations of remission, or toxicities in the dose schedules studied. Irreversible congestive heart failure occurred in five patients with cumulative doses of 240-390 mg/m2. Unless rapid remission induction is urgent, we recommend 60 mg/m2 X four doses and measurement of myocardial function if treatment is to continue.

Autodelen is een zelfversterkend fenomeen dat zich over heel Nederland zal verspreiden, stelt Koen Frenken. Autodelen is de laatste jaren sterk gegroeid, maar de populariteit is nu nog duidelijk geconcentreerd in steden als Amsterdam en Utrecht. Door de dalende kosten bij een groter park van te delen auto’s en door groeiende bekendheid zal het autodelen zich snel buiten de grote steden verspreiden.

In order to determine the clinical applicability of the in vitro observation of enhanced cytotoxicity of 5-fluorouracil (5-FU) in the presence of excess reduced folates, the Southwest Oncology Group (SWOG) performed a randomized trial evaluating two dose schedules of 5-FU and folinic acid (FA) in 128 patients with metastatic colorectal cancer. Of 125 eligible patients, 62 were randomized to receive bolus FA (200 mg/m2 days 1 through 4) in addition to 5-FU (1,000 mg/m2 days 1 through 4) by continuous four-day infusion (infusion arm), while 63 were randomized to receive bolus FA (200 mg/m2 days 1 through 5) in addition to 5-FU (325 mg/m2 days 1 through 5) by bolus injection (bolus arm). The toxicities of the two schedules differed, with stomatitis being more severe in the infusion arm and leukopenia being more severe in the bolus arm. The response rates and survival data for the two arms are nearly identical. The median survival of patients on the infusion arm is 11.0 months and of patients on the bolus arm, 10.3 months. The infusion arm produced one complete response (CR) and 12 partial responses (PRs), for a major response rate of 21% of eligible patients. The bolus arm produced three CRs and 11 PRs, for a major response rate of 22% of eligible patients. The response rate produced is minimally superior to recent cooperative group studies of colorectal cancer, but the response rate and survival experience are within the range of experience for treatment with 5-FU alone.

A prospective randomized trial comparing streptozotocin, mitomycin C, and 5-FU (SMF) with mitomycin C and 5-FU (MF) in patients with advanced pancreatic cancer was performed. In patients with measurable disease the response rates were 34% (19/56) to SMF, and 8% (5/60) to MF (P = 0.009). Median survivals were similar, however, 18 versus 17 weeks (P = 0.356). Median survival of patients responding to chemotherapy was 33 weeks, and for nonresponders it was 17 weeks (P = 0.002). In patients with nonmeasurable disease, median survivals were 21 weeks (SMF) and 18 weeks (MF) (P = 0.797). Patients surviving greater than or equal to 48 weeks, however, appeared to be increased in the SMF arm (14 patients) compared to the MF (7 patients). Toxicity was moderate for both regimens, with SMF having greater gastrointestinal and renal toxicity. Chemotherapy with SMF appears to produce objective responses in patients with pancreatic cancer, but does not improve survival compared to MF.