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Summary Background Advanced pancreatic cancer is a rapidly fatal disease whose course has been little influenced by chemotherapy. Earlier studies have shown some modest promise for the combination of protracted infusional 5-fluorouracil (PIF) and cisplatin. We sought to evaluate a regimen of possibly lesser toxicity, PIF plus weekly carboplatin. Patients and Methods Fifty-four patients with advanced adenocarcinoma of the pancreas were treated with a regimen of protracted infusional fluorouracil 300 mg/m2/day for 70 days and carboplatin 100 mg/m2/weekly on weeks 1 through 10 of a 12-week cycle. After a two-week rest, cycles were repeated until progression. Results Median duration on treatment was 82 days (range 4–490 days). Toxicity was mild. Grade 3–4 toxicities were anemia 11%, leukopenia 6%, thrombocytopenia 2%, nausea/vomiting 7%, diarrhea 9%, mucositis 9%, and renal 2%. Response was evaluable in 47 patients. There were two complete and seven partial responses (17% overall objective response rate among all patients). Stable disease for greater than 12 weeks was seen in 19 patients (40%) and progression in 19 (40%). The median overall survival was 22 weeks (1–99), with 61 weeks median survival in responders (22–99). One-year survival was 13%. Conclusions Response and survival results with this regimen are at least equal to the best combination regimens reported, and were obtained with a low overall rate of serious toxicity.

One hundred eighty-four patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to assess the value of weekly cisplatin (20 mg/m2) when added to a protracted schedule of 5-fluorouracil (5-FU) infusion (PIF) at 300 mg/m2/d for 10 weeks of every 12 weeks. The liver was the primary indicator lesion in approximately 75% of the study group. All tumor measurements required radiographic confirmation. The response rate in the PIF alone arm was 35% (29 of 83; 95% confidence interval [CI], 25% to 46%) compared with 33% (28 of 85; 95% CI, 23% to 44%) for the arm in which weekly cisplatin was added to PIF. The median survival times were 11.8 and 11.2 months in the two groups. Weekly cisplatin does not appear to add to the effectiveness of PIF in colorectal carcinoma.

Twenty-one patients with metastatic colorectal cancer were treated with high-dose intravenous interferon alpha-2 (30-50 X 10(6) units/m2) administered daily for 5 consecutive days. Courses of therapy were repeated every 2 to 3 weeks. No tumor responses were seen among 15 evaluable patients. In two subjects, disease remained stable for 3 and 7 months, respectively. Toxicity was substantial and a de-escalation of dose was frequently required. Fevers, gastrointestinal symptoms, fatigue, leukopenia, and elevated serum transaminases were common. High-dose interferon was found to be ineffective in the treatment of metastatic colorectal cancer. A daily dose of 50 X 10(6) units/m2 was greater than the maximum tolerated dose in this group of patients.

We have conducted a phase I study of the cyclic peptide echinomycin (Quinomycin A) on a schedule of administration of once every 4 weeks. Ten dose levels between 20 and 1800 micrograms/m2 were studied. Acute gastrointestinal toxicity, thrombocytopenia, and transient elevations of serum transaminases occurred at doses of greater than or equal to 1000 micrograms/m2. Gastrointestinal toxicity was severe and dose-limiting in several patients at doses of 1800 micrograms/m2. Thrombocytopenia was erratic, but generally increased with drug doses. Platelet count nadirs occurred 5-10 days after administration. Hepatic toxicity was reflected in transient elevations of serum transaminases without hyperbilirubinemia. Three patients experienced apparent anaphylactic reactions to doses of 1500 micrograms/m2. The maximum tolerated single dose of echinomycin was 1800 micrograms/m2. A starting phase II dose of 1500 micrograms/m2 is recommended.

Thirty-three patients with metastatic malignant melanoma, some of whom had received previous chemotherapy, immunotherapy, or radiotherapy, were entered in a trial of three different doses and schedules of administration of lymphoblastoid alpha interferon. The overall response rate was 9%; some patients had long-lasting response and two achieved complete response. There was no clear advantage to any one regimen. Dose-related flu-like syndrome, granulocytopenia, hepatocellular enzyme elevation, and anemia were observed as the most common toxic effects. Interferon deserves further study in the treatment of malignant melanoma.

The acute aspects of organophosphate poisoning are well understood. Persistent weakness and muscular wasting in some cases have been attributed to neuropathic effects resulting in muscular atrophy from denervation. Recently, necrosis of skeletal muscle has been induced by chronic inhibition of cholinesterase with organic phosphates in a reproducible experimental model. The literature on organophosphate poisoning in man alludes to cases in which it appears plausible to postulate this mechanism as a cause of a residual myopathy. A new case in which chronic organophosphate intoxication may be implicated in the etiology of a proximal myopathy is presented. Reports of additional cases, followed up from the onset of symptoms, are needed to determine whether primary myopathic effects are a clinically significant complication of chronic organophosphate poisoning.