In 1983, the Northern California Oncology Group (NCOG) instituted a randomized trial of intravenous (IV) versus intraarterial (IA) floxuridine (FUDR) administered via an implantable pump for patients with colorectal cancer metastatic to the liver. The study objectives were to compare the hepatic response rate, time to hepatic progression, and toxicity for the two treatment arms. The study design, which allowed patients failing IV FUDR to crossover to the IA arm, prevents a meaningful comparative analysis of survival. Patients with liver-only metastases (N = 143) were randomized, 76 to the IV arm and 67 to the IA arm, and 115 patients (65 IV, 50 IA) were fully evaluable. Of the 65 patients in the IV arm, 28 crossed over to IA treatment after failing IV FUDR. The dose-limiting toxicity of IV FUDR was diarrhea, whereas biliary toxicity limited both the dose and duration of IA FUDR therapy. Of the first 25 patients treated with IA FUDR at a dose of .3 mg/kg/day, 10 developed radiographically evident biliary strictures, and three developed permanent jaundice. With reduction of the initial IA FUDR dose to .2 mg/kg/day, and adoption of a policy of early dosage reduction, treatment interruption, or termination of therapy for persistent elevations in alkaline phosphatase, only two further cases of serious biliary toxicity occurred. However, 26 of the 50 IA FUDR patients ultimately had therapy terminated because of drug toxicity rather than disease progression. When compared with systemic infusion, infusion into the hepatic artery greatly enhanced the antitumor activity of FUDR against colorectal liver metastases. Although biliary toxicity is the most serious limitation of this form of therapy, biliary stricture and jaundice usually can be averted through careful monitoring of liver enzymes and early dosage reduction.
A novel foam formulation with enhanced BMV bioavailability has been shown to be of increased efficacy in the treatment of scalp psoriasis without an associated increase in toxicity.
Fifty-eight patients with metastatic transitional cell carcinoma of the urinary tract received cisplatin, methotrexate, and vinblastine (CMV) combination chemotherapy. Complete responses (CRs) were noted in 14 of the 50 (28%) evaluable patients and partial responses (PRs) in 14 patients for an overall response rate of 56% (95% confidence limits of 42% to 70%). The median duration of the 14 CRs was 9 months. Six of the 14 CRs (43%) remain in unmaintained remission from 6 + to 35 + months from onset of treatment. The median survival of evaluable patients receiving CMV was 8 months. Median survival for CRs was 11 months v 7 months for PRs (P less than .05) and 6 months for nonresponders. Renal and hematologic toxicities with this regimen were moderate. CMV is an effective regimen for patients with metastatic transitional cell carcinoma of the bladder. Prolonged disease-free survival may result from a CR to this regimen.
Forty-nine patients with locally advanced carcinoma of the pancreas were treated in a randomized, prospective study comparing definitive helium ion radiation therapy with conventional split-course megavoltage photon irradiation. Patients in each treatment arm underwent exploratory staging laparotomy followed by concurrent radiation therapy and 5-fluorouracil chemotherapy. Patients treated with photons received 6,000 cGy over a period of 10 weeks; patients treated with helium irradiation received a 6,000-7,000-cGy-equivalent dose over a period of 8-9 weeks. There was no significant difference in overall survival between patients in the two treatment arms (P = .29). Patients treated with helium ions had a slightly longer median survival (7.8 months) than the photon-treated patients (6.5 months). Local control rates were slightly higher in the helium-treated patients (10% vs 5%). Complications included one chemotherapy-related death. Four of the five helium-treated patients who survived longer than 18 months died of local failure without distant metastases. These results suggest that more aggressive local therapy could result in improved survival in helium-treated patients.
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