Bernard Kabakow

Improved therapy with cisplatin regimens for patients with ovarian carcinoma (FIGO Stages III and IV) as measured by surgical end-staging (second-look operation)

Between 1974 and 1982, 273 patients with epithelial cancer of the ovary (International Federation of Gynaecology and Obstetrics Stages III and IV) were randomized in four therapeutic trials. In Trial I Adriamycin plus cisplatin versus cisplatin alone versus thiotepa plus methotrexate was tested. The superiority of Adriamycin plus cisplatin in producing the best response rate led to its use as the reference arm in subsequent trials. All investigational arms included cisplatin plus other drugs (cyclophosphamide, Adriamycin, hexamethylmelamine, and thiotepa) in various combinations. Eligibility for second look required complete clinical remission and completion of at least 10 cycles of chemotherapy. To date, 73 second-look operations have been performed on randomized patients. An additional 43 nonrandomized patients underwent second-look procedures and are analyzed separately. Between 40% and 46% of patients treated with cisplatin regimens had no disease at second look. Cell differentiation and volume of postoperative disease did not influence response.

High-dose platinum for the treatment of refractory ovarian cancer.

Abstract High-dose cis -diamminedichloroplatinum, 120 mg/m 2 , produced six clinical responses (three complete) for 12 patients with advanced ovarian adenocarcinoma failing initial therapy with an alkylating agent. Responders survived 8+ to 20+ months. The same dosage produced four (zero complete, one short) responses for 20 patients refractory to a 50 mg/ m 2 dosage. Ten instances of nephrotoxicity and five of neurotoxicity were apparently related to a total cumulative dose of DDP and were predominantly seen in patients with prior DDP therapy and in patients with maintained responses to high-dose DDP.

Cisplatin regimens and improved prognosis of patients with poorly differentiated ovarian cancer.

Patients with advanced ovarian carcinoma, Stage III or IV (International Federation of Gynaecology and Obstetrics), were randomized to primary chemotherapy with doxorubicin (Adriamycin) and cisplatin plus or minus hexamethylmelamine, and cyclophosphamide (CHAP). The four-drug CHAP regimen produced a 57% complete clinical response rate and a 26% partial response rate for clinically evaluable patients. The median survival of CHAP patients is 25 months. The two-drug Adriamycin-cisplatin (AP) regimen produced a 43% complete response rate and a 35% partial response rate. The median survival is 18 months. The four-drug regimen produced a significantly longer median survival (28 versus 18 months) for patients with poorly differentiated tumors than for patients with well-differentiated tumors on either treatment. Examination of treatment failure or death by treatment, histology, and size of largest residual tumor and comparison to similar patients treated with AP in this and two preceding controlled trials also suggest that CHAP is superior to AP for patients with poorly differentiated tumors.

Triple combination chemotherapy of disseminated melanoma

Sixteen patients with disseminated malignant melanoma were treated with triple combination chemotherapy consisting of vincristine, BCNU, and imidazole carboxamide. Ten of 16 patients (62.5%) showed significant response, including two complete responses. These two patients have remained in a state of no measurable disease for 9 and 14 months. Responses were seen in cutaneous, lymph node, and pulmonary metastasis. The two osseous and two hepatic metastases were unaffected by therapy. Even though the drug dosage (especially of the BCNU) was greater than in previous reported studies, the morbidity was acceptable and there was no mortality. The response rate of 62.5%, even in this small group of patients, warrants further study of this combination approach in the treatment of disseminated malignant melanoma.

Treatment of chemotherapy-resistant advanced ovarian cancer with a combination of cyclophosphamide, hexamethylmelamine, adriamycin, and cis-diamminedichloroplatinum (CHAP)☆

Abstract A four-drug regimen consisting of cyclophosphamide, hexamethylmelamine, adriamycin, and cis -diamminedichloroplatinum (II) (CHAP) produced three complete clinical and seven partial responses for 21 patients with adenocarcinoma of the ovary after objective progression of disease during treatment with standard chemotherapy. Median survival was 15 months for responders and 7 months for all patients.

Chemotherapy of recurrent ovarian carcinoma with cis-dichlorodiammine platinum II and adriamycin.

Forty-six patients with recurrent disseminated ovarian carcinoma were treated with a combination of cis-dichloro-diammine platinum II (DDP) 50 mg/m2 and adriainycin 50 mg/m2 given intravenously every 3 weeks. All patients had failed prior chemotherapy. The combination of adriamycin and DDF produced objective responses in 14 of 46 patients. Severe side effects were frequent, but no patient died as a result of treatment. Disease in 4 of 7 complete responders is currently in remission up to 4 years.

Intravenous chemotherapy with concurrent peritoneal dialysis: Continued treatment of ovarian carcinoma after drug toxicity

Abstract Despite the frequent response of disseminated ovarian carcinoma to chemotherapy, toxicity to other organs, especially bone marrow, limits the potential for remission and survival in these patients. An attempt has been made to extend survival in those patients with ovarian carcinoma in whom a remission had been achieved, but depressed bone marrow limited conventional administration of antitumor drugs. Seventeen patients with disseminated ovarian carcinoma and toxicity to prior treatment with thio-tepa have received further intensive intravenous chemotherapy with concurrent peritoneal dialysis. Tolerance to the technique has been good with low toxicity. Further intravenous chemotherapy with concurrent peritoneal dialysis is recommended in responding cases when toxicity would otherwise curtail administration of the active drug, thio-tepa.

Subcutaneous emphysema secondary to perforated radiation proctosigmoiditis.

Abstract An apparently unique case history of subcutaneous emphysema presenting in the head and neck arising from perforated radiation proctosigmoiditis is reported.