Phase II trial of adjuvant radiation and intraperitoneal 5-fluorouracil for locally advanced colon cancer: results with 10-year follow-up.

PURPOSE: To determine the toxicity, disease-free survival, and overall survival for patients with Modified Astler-Coller (MAC) B2-3 or C1-3 colon cancer receiving adjuvant radiation and sequential intraperitoneal 5-fluorouracil (5-FU). METHODS AND MATERIALS: From August 1984 to June 1989, 45 patients were accrued to this Phase II trial and received a 21-week course of intraperitoneal 5-FU (20 mg/kg/d x 5) and external beam radiation. The radiation was delivered to the tumor bed and para-aortic lymph nodes in two split-courses of 22.5 Gy, alternating with the first two cycles of chemotherapy. All patients then received 4 additional cycles of intraperitoneal 5-FU. RESULTS: The therapy was well tolerated with 4 patients experiencing Grade 3 peritonitis. Four patients developed small bowel obstruction requiring surgery; in each instance, recurrent tumor was found at the time of laparotomy. The median and overall survivals at 10 years were 9.3 months and 53% respectively. Local failures were infrequent, occurring in only 11% of patients treated. CONCLUSIONS: Sequential intraperitoneal 5-FU and tumor-bed/para-aortic irradiation is tolerable in patients with resected colon cancer. Although the incidence of local and regional relapse appeared to be lower than anticipated, this did not appear to translate into improved survival.

Randomized comparison of the antiemetic efficacy of a serotonin type 3 receptor antagonist (MDL 72,222) with a high-dose metoclopramide regimen.

This pilot randomized study compared MDL 72,222, a highly selective 5-HT3 receptor antagonist, with a high-dose metoclopramide regimen (HDM) for chemotherapy-induced nausea and vomiting. MDL 72,222 was given in 20 mg intravenous doses 30 minutes before chemotherapy, as well as 2, 6, and 12 hours after chemotherapy infusion. The HDM was composed of diphenhydramine 50 mg i.v., metoclopramide 2 mg/kg i.v., and lorazepam 0.04 mg/kg i.v. administered 30 minutes before chemotherapy and 2, 4, 6, and 8 hours after chemotherapy. Patients were randomized to either MDL 72,222 (n = 12) or the HDM (n = 12) and were matched for age, weight, Karnofsky performance status, and chemotherapy. More patients in the MDL 72,222 group had received prior cisplatin. The MDL 72,222 group and the HDM group received a mean cisplatin dose of 66 mg/m2 and 62 mg/m2, respectively. Patients were observed for retching and/or emesis for 24 hours and completed a visual analog scale (VAS) for nausea. Six MDL 72,222 and five HDM patients had no vomiting. One MDL 72,222 and two HDM patients had one episode of emesis within 24 hours of chemotherapy. The median number of emetic episodes in the first 24 hours was 0.5 for MDL 72,222 and 1.0 for HDM patients. HDM patients were frequently asleep and were not awakened for evaluation of nausea with the VAS; 58% (70 of 120) of the HDM (mean score: 19.1 mm) and 14% (17 of 119) of the MDL 72,222 (mean score: 17.1) patients could not have VAS scores obtained (X2 = 50.74, p < 0.001). MDL 72,222 had similar efficacy with less sedation, and further trials are warranted.

Randomized comparison of cisplatin plus epirubicin or doxorubicin for advanced epithelial ovarian carcinoma. A multicenter trial.

Stage III and IV epithelial ovarian cancer patients were prospectively randomized to receive eight courses of 60 mg/m2 of cisplatin plus either 75 mg/m2 of epirubicin (62 patients) or 60 mg/m2 of doxorubicin (54 patients). Clinical response rates for cisplatin/epirubicin of 42% [15% complete response (CR) and 27% partial response (PR)] and for cisplatin/doxorubicin of 55% (24% CR and 31% PR) were not statistically different (p = 0.14). The negative second look rate was 35% (10/29) for cisplatin/doxorubicin and 17% (5/30) for cisplatin/epirubicin (p = 0.12). The progression-free interval for cisplatin/epirubicin (13 months) was not statistically different (p = 0.09) from that for cisplatin/doxorubicin (19 months). The median survivals for cisplatin/epirubicin (756 days) and cisplatin/doxorubicin (739 days) were similar (p = 0.70). Cardiotoxicity was greater for the cisplatin/doxorubicin group (p = 0.0003). With similar survival and less cardiotoxicity, the cisplatin/epirubicin regimen had the more favorable therapeutic index.

Chemotherapy of advanced ovarian epithelial carcinoma with melphalan and levamisole: a pilot study of the Gynecologic Oncology Group.

Twenty-three patients with Stage III, Stage IV, or recurrent epithelial ovarian cancer were treated with a combination of melphalan and levamisole to determine a tolerable dosage schedule, possible adverse effects, and a general estimate of response rate and duration. In seven patients with measurable disease there were four complete responses (57%) with a median duration of 75 weeks. Two of the complete responders have had negative second-look laparotomies while the other two patients have had subsequent progression. Of 16 patients with nonmeasurable disease two have had negative second-look laparotomies and two remain progression free. Thus 8 of 23 patients (35%) had complete responses or remain progression free whereas 4 of 23 patients (17%) have had negative second-look laparotomies. No serious toxicity was encountered. Immunologic monitoring did not indicate significant immunologic reconstitution in these immunosuppressed patients.