The appearance of autoantibodies or clinical manifestations of autoimmunity during treatment with interferon alfa-2b is associated with statistically significant improvements in relapse-free survival and overall survival in patients with melanoma.

We have retrospectively evaluated and characterized the hypersensitivity reactions associated with carboplatin administration in ovarian cancer patients treated mainly on an outpatient basis at the Laikon Hospital from 1988 to 1998. A total of 240 patients, who had never been exposed to platinum compounds previously, received carboplatin plus cyclophosphamide (n = 58) or paclitaxel (n = 136) intravenously, and intraperitoneal carboplatin plus intravenous cyclophosphamide (n = 46). The median number of carboplatin courses was 6 (range 3–12) and 5 (range 4–6) for the intravenous and intraperitoneal treatment regimens, respectively. Thirty-two of 194 patients (16%) who were on intravenous carboplatin treatment developed symptoms compatible with a hypersensitivity reaction to carboplatin, that was always verified by manifestation of at least similar symptoms on rechallenging. In contrast, in the group of 46 patients on intraperitoneal carboplatin treatment, no hypersensitivity reaction was ever noticed. Hypersensitivity reactions always occurred after administration of the first 4 intravenous courses of carboplatin; 4, 19, 4, and 5 reactions occurred at the 5th, 6th, 7th, and 8th courses, respectively. These reactions could be distinguished in: (a) mild hypersensitivity reactions in 20 of 194 patients, which manifested as itching (20 patients) and small area erythema plus erythema of the palms and soles (12 patients), occurring either during intravenous injection when most of the drug scheduled had been administered, or within 3 days, and (b) in severe reactions in 12 of 194 patients, which manifested acutely as itching, diffuse erythroderma, rigor, facial swelling, throat and chest tightness, tachycardia (12 patients) and bronchospasm (2 patients), and hypertension or hypotension in 8 and 4 patients, respectively. With appropriate symptomatic management, discontinuation of carboplatin treatment was not required in patients with mild hypersensitivity reactions, but none of the 12 patients with severe reactions was able to receive a full subsequent dose of carboplatin on rechallenging. However, in 4 of these 12 patients carboplatin was replaced by cisplatin, which was given for 4–6 courses without side effects. These findings indicate that although hypersensitivity reactions are common in general, occurring in almost 1 of every 6 patients treated intravenously with carboplatin, their clinical picture is variable, leading to discontinuation of treatment in only 6% of patients. This is not the case when the intraperitoneal route of carboplatin administration is used when indicated.

Cisplatin (C) or carboplatin (CBP) plus cyclophosphamide (CTX) was until recently considered standard chemotherapy for advanced ovarian cancer (OC). Attempts to maximize platinum and its analog activity against OC include its administration directly into the peritoneal cavity. In the past we have shown that intraperitoneal (IP) CBP administration is a safe and effective treatment for OC [Polyzos et al: Proc Am Assoc Cancer Res 1990;31: 1120]. In the present study we aimed to compare the effectiveness and toxicity of CBP administration either intravenously (IV) or IP plus CTX IV. Since 1990, 90 evaluable patients with stage III OC were prospectively randomized to receive CBP 350 mg/m² IV or IP plus CTX 600 mg/m² IV (in both groups) every 3–4 weeks for six courses. The randomization incorporated stratification according to performance status and the amount of residual tumor (maximum diameter ≤2 or >2 cm). Clinical assessment was performed with abdominal CT and serum CA-125. Responses were observed in 33/46 = 72% (95/CI 56.5–84.0) of the IV group and in 33/44 = 75% (95/CI 59.7–86.8) of the IP group with 48 and 45% clinical complete responses, respectively. Times to progression were 19 months (8–62+) for the IV group and 18 (6–72+) for the IP group. Median survivals were: 25 months (6–80+) and 26 months (6–72+), respectively. Significantly more patients in the IV group than in the IP group had grade 3 or higher leukopenia (p < 0.01) and grade 3 thrombocytopenia (p < 0.09). Morbidity due to infectious complications in the IP group was minimal. It seems that IP CBP is equally effective to IV administration in terms of response and survival with less myelotoxicity. The favorable results on survival demonstrated in studies with IP C administration in patients with small volume disease [Alberts et al: N Engl J Med 1996;335:1950–1965] could not be repeated in the present study applying CBP in patients with variable tumor size and a relatively small number of patients. The likelihood that patients with large volume disease would benefit from a regional approach compared to systemic administration is small and this explains the inability to detect a difference between the two arms.

DC regimen resulted in a higher response rate but without improvement in median time to tumor progression or OS compared with D. D could be a reasonable front-line chemotherapy for patients who cannot tolerate cisplatin.