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Purpose: NRG Oncology RTOG 9704 was the first adjuvant trial to validate the prognostic value of postresection CA19-9 levels for survival in patients with pancreatic carcinoma. The data resulting from this study also provide information about predictors of recurrence that may be used to tailor individualized management in this disease setting. This secondary analysis assessed the prognostic value of postresection CA19-9 and surgical margin status (SMS) in predicting patterns of disease recurrence. Methods and materials: This multicenter cooperative trial included participants who were enrolled as patients at oncology treatment sites in the United States and Canada. The study included 451 patients analyzable for SMS, of whom 385 were eligible for postresection CA19-9 analysis. Postresection CA19-9 was analyzed at cut points of 90, 180, and continuously. Patterns of disease recurrence included local/regional recurrence (LRR) and distant failure (DF). Multivariable analyses included treatment, tumor size, and nodal status. To adjust for multiple comparisons, a P value of ≤ .01 was considered statistically significant and > .01 to ≤ .05 to be a trend. Results: For CA19-9, 132 (34%) patients were Lewis antigen–negative (no CA19-9 expression), 200 (52%) had levels

Malignant melanoma is increasing in frequency at a rapid rate in the United States. Metastatic disease is chemoresistant with DTIC considered the most active single agent. CI-980 is a synthetic mitotic inhibitor that blocks the assembly of tubulin and microtubules. It has shown cytotoxic activity against a broad spectrum of murine and human tumor cell tines. CI-980 can cross the blood brain barrier, is effective when given orally or parenterally, and is active against multidrug resistant cell lines overexpressing P-glycoprotein. In this trial, patients with disseminated melanoma with measurable disease, SWOG performance status of 0-1, no prior chemotherapy or immunotherapy for metastatic disease, and adequate hepatic and renal function, were enrolled. Treatment with CI-980 was given by 72 h continuous i.v. infusion at a dose of 4.5 mg/m2/day, days 1-3 every 21 days. Twenty-four patients were registered on this study with no patients ineligible. They ranged in age from 33-78 with performance status of 0 in 15 patients and 1 in 9 patients. Nineteen patients had visceral disease with 12 having liver involvement. There were no confirmed responses. The overall response rate was 0% (95% CI 0%-14%). The median overall survival is eleven months (95% CI 4-14 months). The most common toxicities were hematologic and consisted of leukopenia/granulocytopenia and anemia, with nausea/vomiting and malaise/fatigue/weakness also frequent. CI-980 administered at this dose and schedule has insufficient activity in the treatment of disseminated malignant melanoma to warrant further investigation.

The genetically determined ability to metabolize the antihypertensive drug debrisoquine has been proposed as a genetic risk factor for primary carcinomas of the lung. To test this hypothesis, the metabolism of the drug was evaluated in a case control study. The subjects were characterized by their ability to metabolize debrisoquine after receiving a test dose of the drug followed by the collection of an 8-hour urine sample. They were classified by laboratory analysis into one of the following three groups: extensive, intermediate, and poor metabolizers. Poor metabolizers comprise 10% of the population and are unable to hydroxylate the drug. This group was expected to be at highest risk for deleterious effects from this medication. A protocol was created that included patient education and blood pressure monitoring to administer this medication safely to a group of patients with cancer who were already compromised. Although poor metabolizers showed a small decrease in systolic and diastolic blood pressure, no significant hypotensive episodes or clinical sequelae were observed in any of the groups. These data suggest that debrisoquine can be administered safely in a controlled clinical setting and will be useful for the characterization of lung cancer patients in biochemical epidemiology studies.

The authors have used imidazole carboxamide (DTIC) in vascular isolation and hyperthermic perfusion for melanoma. The regional and systemic toxicity and complications of this procedure were studied in 40 cases with Stage III (15) and Stage I (25) melanoma. Technetium 99m-labelled serum albumin crossover and pharmacokinetic studies were done simultaneously to see if these correlate with toxicity. Local toxicity on muscles, nerves, skin, and arteries was conspicuously absent despite using dosages of 2 g/m2 (40-45 mg/kg) for the lower extremity and 1.2 g/m2 (24-28 mg/kg) for the upper extremity. Skin and core temperature were raised to 39 degrees C to 40 degrees C. Deep vein thrombosis was noted in three patients. No death or gangrene of the extremities occurred. Local infection was noted in only one patient. Fourteen patients (35%) manifested bone marrow toxicity (leukocyte count of 4000/mm3 or platelets of 100,000/mm3) in the second or third week after perfusion. Severe hematologic toxicity was seen in two instances. Dosages of DTIC greater than 40 mg/kg were associated with toxicity in 65% of the patients. No bleeding complications occurred in seven patients with thrombocytopenia. Measurement of crossover and recovery of radionuclide were not reliable indicators of subsequent systemic toxicity. Perfusion fluid balance data also were of no predictive value. Forty-seven percent of the administered DTIC was recovered in washout fluid. Of this, less than 2% was converted to its metabolites, that is aminoimidazole carboxamide and 2-azahypoxanthine. Thirty-five of 40 patients experienced mild nausea and vomiting. Transient and mild hepatotoxicity was noted in seven patients. It appears that DTIC hyperthermic isolation perfusion is a safe procedure, however, the total dosage should be below 40 mg/kg to avoid hematologic toxicity.

Eighty-eight cancer patients with the presence of one or more adverse factors for healing (carcinomatosis, adhesions, prior chemotherapy and radiation therapy, bowel obstruction, anemia, and low leukocyte count or albumin value) were prospectively randomized to undergo conventional two-layer hand suturing (45 patients) or mechanical stapling with a GIA/TA instrument (U. S. Surgical Corp., Norwalk, CT) (43 patients) of the large or small bowel anastomosis. Age, sex, complete blood count findings, and all biochemical plasma values were comparable in both groups. The anastomosis took an average of 19 minutes for the sutured and 9 minutes for the stapled technique (P = 0.0001), but the average length of operation, postoperative return of bowel function, and hospital stay were comparable in both groups. Bowel fistula was seen in one case of stapled anastomosis (P = not significant). The pulmonary and wound complication rates were the same in both groups. Of the four deaths (4.5%) due to causes unrelated to bowel anastomosis, three occurred in the stapled and one in the sutured group. It was concluded that a stapled anastomosis is as safe as a sutured one in patients with advanced-stage cancer. It saves time in anastomosis, but does not save time in postoperative return of the bowel function and hospital stay.