Biomedical subjects
Publications and source records attributed to R E Slayton.
Based upon the activity observed in this trial, there does not appear to be a significant role for AZQ as a salvage agent for leiomyosarcoma of the uterus at the dose and schedule tested.
AZQ was given intravenously to 23 patients with mixed mesodermal sarcoma of the uterus refractory to conventional treatment at a dose of 22.5-30 mg/m2 q three weeks. There was one partial response lasting seven weeks and one drug-related death. Based upon the activity observed in this trial, there does not appear to be a significant role for AZQ as a salvage agent for mixed mesodermal sarcomas of the uterus at the dose and schedule tested.
Twenty-six patients with recurrent adenocarcinoma and adenosquamous carcinoma of the uterine cervix were treated with diaziquone (AZQ) 22.5 mg/m2 diluted in 150 ml normal saline every three weeks. In the absence of adverse effects the second dose and all subsequent doses were escalated to 30 mg/m2. All patients had measurable disease and only 11 had received prior chemotherapy. Two partial responses were noted among 15 patients with no prior chemotherapy, while no responses were observed among 11 previously treated patients. The major toxicity was leukopenia and thrombocytopenia. Median progression-free interval was 1.5 months and median survival was 4 months. AZQ displays minimal activity against recurrent nonsquamous carcinoma of the cervix at the dose and schedule used.
Extragonadal germ cell tumors may have a worse prognosis than germ cell tumors of gonadal origin, even when tumor bulk and extent of dissemination are equal. Primary retroperitoneal pure choriocarcinoma is one of the least common subgroups of the extragonadal germ cell tumors and has previously appeared to have the worst prognosis. Two new case reports on the treatment and follow-up of two patients with primary retroperitoneal pure choriocarcinoma are discussed. Both patients are disease-free at 24 and 81 months, respectively. After aggressive primary multiagent drug therapy for primary retroperitoneal pure choriocarcinoma, a favorable prognosis may be anticipated.
Twenty-six patients with measurable endometrial cancer refractory to standard therapy received AZQ [1,4-cyclohexadiene-1,4-dicarbamic acid, 2,5-bis(1-aziridinyl)3,6,dioxo,diethyl ester, NSC 182986] 22.5 mg/m2 diluted in 150 ml normal saline intravenously every three weeks. Thirteen patients experienced no toxicity and the dose in those patients was increased to 30 mg/m2 after the first course. The median number of courses given was 2.5 (range 1-9). The leukocyte count fell below 3000/microliter in 12 patients, and below 1000/microliter in two. The platelet count fell below 100,000/microliter in 12 patients, and below 25,000/microliter in one. Cumulative hematologic toxicity was not seen. One clinical complete response and one partial response were observed. Eight patients had stable disease. Median time to disease progression was 2 months. Median survival was 5.9 months. At this dose and schedule AZQ does not appear to have significant activity in recurrent endometrial cancer.
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Seventy-six patients with malignant germ cell tumors of the ovary received vincristine, dactinomycin, and cyclophosphamide (VAC) postoperatively. Fifty-four were treated after removal of all gross disease. The majority of these remain disease-free. Indeed, only 15 (28%) have failed, including 11 of 24 with pure endodermal sinus tumor, 3 of 11 (27%) with mixed germ cell tumor containing endodermal sinus elements, and only 1 of 20 with immature teratoma grade 2 or 3, a patient seen initially with recurrent disease. Postoperative VAC therapy, however, did not appear to be effective in patients with unresectable or incompletely resected germ cell tumors of the ovary. Fifteen of 22 patients (68%) with incompletely resected germ cell tumors failed VAC therapy, including 4 of 7 with pure endodermal sinus tumor, 5 of 5 with mixed germ cell tumors containing endodermal sinus elements, 2 of 2 with embryonal carcinoma, and 4 of 8 with immature teratoma. In failing, patients' median time to progression was 8 months. Dose-limiting toxicity was seen in 30% of the entire group. Combined cisplatin, vinblastine and bleomycin therapy now is being tested in this group of tumors.
This report analyzes six ovarian Sertoli-Leydig cell tumors that showed retiform differentiation. The patients were young (6-29 years; average age, 17). The tumors were all limited to one ovary, and the patients have remained disease-free, with one exception, a patient who died of recurrent neoplasm 3.5 years after operation. On microscopic examination, the retiform areas were predominant in three cases and focal in the other three. The retiform areas consisted of an irregular anastomosing network of spaces lined by cuboidal cells, often with papillary formations and sometimes with tubules compressed to form slit-like spaces. In three cases the retiform areas appeared mature, and in three they were less differentiated. All tumors also had areas of typical Sertoli-Leydig cell tumor of either poor or intermediate differentiation. In the patient with metastatic disease, the metastases had a pure sarcomatoid pattern without any retiform areas.
From October 1978 to October 1981, 135 patients with disseminated transitional cell carcinomas of the urinary tract, with either measurable or evaluable disease, were randomized to receive either cis-diamminedichloroplatinum (DDP) or cyclophosphamide (CTX), Adriamycin (ADR) (Adria Laboratories, Columbus, Ohio), and DDP (CAD). DDP was given at a dose of 60 mg/m2, CTX at 400 mg/m2, and ADR at 40 mg/m2 intravenously every three weeks. Patients over the age of 65 and those with prior radiation received 75% of the dose initially. The dose was escalated if only mild toxicity developed. Of the patients on the CAD arm, 34% developed grade 3 or 4 hematologic toxicity, as compared to 3% in patients on the DDP therapy. Of the 93 patients with measurable disease, 48 received DDP. Seventeen percent had a partial or complete remission, as compared to 33% of the 45 patients on the CAD arm (P = .09). The crude median survival of patients on DDP was 6.0 months as compared to 7.3 months in patients receiving CAD (P = .17). We conclude that the CAD combination is more toxic than DDP with, at best, very marginal benefit in survival.
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