Robert F. Asbury

Goserelin acetate as treatment for recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

This Gynecologic Oncology Group (GOG) study was designed to estimate the activity of goserelin acetate as treatment for advanced and recurrent endometrial carcinoma. Forty evaluable patients received monthly treatment with goserelin acetate at a dose of 3.6 mg, given subcutaneously. Standard GOG response and adverse effects criteria were used. The median age of patients was 71 years. Seventy-one percent of patients had received prior radiation therapy; 18% of patients were reported to have received prior progestational therapy for endometrial cancer. One patient had received prior chemotherapy. There were two complete responses (5%) and three partial responses (7%). One response occurred in a patient who previously did not respond to progestin therapy after having achieved a response. The overall response rate was 11% (95% CI: 4–27%). Median progression-free survival was 1.9 months and median overall survival was 7.3 months. No severe or life-threatening toxicities occurred because of goserelin. Deep venous thrombosis developed in two patients. This study confirmed the limited activity of goserelin acetate in endometrial carcinoma, with only one response in a patient previously treated with hormonal therapy. The activity is insufficient to warrant further study of the single agent at this time. Elucidation of the mechanism of action of this drug may allow more effective use in conjunction with other agents in the future.

Comparing the effectiveness of behavioral treatment for chemotherapy-induced nausea and vomiting when administered by oncologists, oncology nurses, and clinical psychologists.

Adequate control of side effects during medical treatment of cancer increases patient compliance and quality of life. Antiemetic drugs are not an effective treatment for the one in three cancer patients on chemotherapy who experience anticipatory nausea and vomiting (ANV); the behavioral treatment of systematic desensitization has been found effective for ANV when delivered by clinical psychologists. This study examined the effectiveness of systematic desensitization when delivered by medical personnel versus clinical psychologists. Seventy-two consecutive cancer patients with ANV were randomly assigned to no-treatment control or to systematic desensitization from 5 behaviorally trained clinical psychologists, 6 clinical oncologists, or 10 oncology nurses. The treatment was found effective in reducing anticipatory nausea, anticipatory vomiting, posttreatment nausea, and posttreatment vomiting compared to control patients, with no significant differences in effectiveness found between clinical psychologists and oncology staff. Although medical personnel should not engage patients in psychotherapy or other interventions that cannot be completed successfully, they can treat patients effectively with systematic desensitization and should be encouraged to learn and use this and other behavioral intervention techniques to benefit total patient care.

Treatment of metastatic breast cancer with aminoglutethimide

Seventy‐three women with metastatic breast cancer were treated with aminoglutethimide and dexamethasone. No complete responses occurred. Ten patients (16%) achieved partial responses (mean duration, 12 months). The proportions of patients responding by disease site were breast (50%), nodes (33%), skin (23%), bone (16%), lung (11%), and liver (7%). Response did not correlate with age, menopausal status, performance status, or cortisol suppression. Ninety percent of responders had had previous responses to hormonal manipulations. No responses occurred in estrogen receptor negative patients. An additional 20% of patients had disease stabilization of eight or more months (mean, 17 months). Severe bone pain was present in 47 patients and was relieved in 19. Side effects occurred in 75% but caused discontinuation of therapy in only four patients. Somnolence, nausea, rash, Cushings syndrome, and leukopenia were the most frequent side effects. Aminoglutethimide with dexamethasone is an effective hormonal treatment for metastatic breast cancer.

A phase II trial of aminothiadiazole in patients with mixed mesodermal tumors of the uterine corpus : A Gynecologic Oncology Group study

Aminothiadiazole (NSC 4728) is an analog of the thiadiazoles, a group of drugs that stimulated interest because they do not cause significant myelosuppression and have a unique ability to increase uric acid production unrelated to tissue damage. Previous articles have reported results in ovarian cancer, squamous cell cervical cancer, nonsquamous cell cervical cancer, and endometrial cancer. The Gynecologic Oncology Group chose to study aminothiadiazole in patients with mixed mesodermal tumors of the uterus refractory to prior chemotherapy. Twenty-two patients were entered into this study. Eligibility required that patients had histologically confirmed measurable malignancy. All patients received a starting dose of aminothiadiazole of 125 mg/m2 intravenously (30-45 min infusion) repeated at weekly intervals. All patients also took allopurinol, 300 mg orally per day, to prevent hyperuricemia. Subsequent therapy was not given unless the white blood cell count was > 3,000/microliters and platelets were > 100,000/microliters prior to treatment. One patient (5%) in this study had a partial response, which lasted only 1.2 months. The site of this response was a mesenteric mass. Most patients in this study had no toxicity whatsoever, and no life-threatening toxicity was seen. There were no complete responses. Aminothiadiazole in this dose schedule appears to have no utility in previously treated patients with mixed mesodermal tumors of the uterus.

Amonafide in patients with leiomyosarcoma of the uterus: A phase II gynecologic oncology group study

Twenty-six evaluable patients who had leiomyosarcoma of the uterus were treated with amonafide, 300 mg/m2, for 5 consecutive days every 3 weeks. One partial response (4%) resulted. Hematologic toxicity was substantial, with grade 3 or 4 events occurring as follows: leukopenia, 12 patients (46%); thrombocytopenia, 4 patients (15%); and granulocytopenia, 7 patients (27%). One patient had transient grade 4 renal failure. Considering the poor activity and substantial toxicity that was observed, no further studies are planned by the Gynecologic Oncology Group using amonafide at this dose schedule in leiomyosarcomas.

A randomized Phase II study of interleukin-2 with and without beta-interferon for patients with advanced non-small cell lung cancer: An Eastern Cooperative Oncology Group study (PZ586)

Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are biologic agents with antitumor activity observed in preclinical models. Some studies of patients with advanced non-small cell lung cancer treated with IL-2 report relatively long survival, despite low response rates. Seventy-six evaluable patients with stage IV non-small cell lung cancer were treated in a randomized Phase II study with either IL-2 alone or IL-2 plus beta-IFN. Patients received either IL-2 at 6 x 10(6) Cetus units/m2 3 days weekly or the combination of IL-2 at 5 x 10(6) Cetus units/m2 plus beta-IFN at 6 x 10(6) units/m2, both given 3 days weekly. Both biologic agents were administered by intravenous bolus injection on an outpatient basis. Objective responses were observed in 3/76 (4%)) patients. Grade 4 toxicity occurred in 3/39 patients treated with IL-2 alone, and in 4/37 patients treated with IL-2 plus beta-IFN. An additional lethal respiratory toxicity occurred in a patient who received IL-2 plus beta-IFN. The median survival of all patients treated on this study was 33 weeks. Despite producing only a 4% objective response rate. IL-2 appears to have a favorable impact on survival comparable to chemotherapy. The role for this immune therapy in the management of non-small cell lung cancer requires further study.

Aminothiadiazole in the treatment of advanced leiomyosarcoma of the uterine corpus. A Gynecologic Oncology Group study.

Aminothiadiazole was used to treat 21 patients with metastatic or recurrent leiomyosarcoma of the uterus. All patients received a starting dose of aminothiadiazole of 125 mg/m2 intravenously (30− to 45-minute infusion), which was repeated at weekly intervals. All patients also took allopurinol 300 mg per day orally to prevent hyperuricemia, a side effect of aminothiadiazole. Five patients (25%) had stable disease but there were no objective responses. Toxicity was generally mild with this regimen. There was no life-threatening toxicity and only three episodes of severe toxicity. One patient experienced both grade 3 leukopenia and thrombocytopenia, while another patient had grade 3 nausea and vomiting. Further studies in this disease are not planned.

Aminothiadiazole (NSC 4728) in patients with advanced carcinoma of the endometrium : a phase II study of the gynecologic oncology group

Twenty-one evaluable patients with advanced carcinoma of the endometrium were treated with aminothiadiazole at a dosage of 125 mg/m2 weekly. Twelve had received prior chemotherapy. Seven patients had stable disease; 14 had increasing disease. There were two life-threatening toxic episodes. Aminothiadiazole used in this dosage and schedule has negligible activity in previously treated patients with carcinoma of the endometrium.

Effect of Cisplatin on Myoelectric Activity of the Stomach and Small Intestine in Dogs

The effect of cisplatin on interdigestive myoelectric activity (IDMA) of the gastric antrum, duodenum and jejunum, plasma concentration of motilin, and animal behavior was studied in seven conscious dogs with gastric cannulas and platinum electrodes implanted on the serosal surface of antrum and upper small intestine. Cisplatin given intravenously in a dose of 2 mg/kg resulted in complete interruption of IDMA and produced predominantly phase II-like activity, lasting as long as 24 hr. Six of the seven dogs exhibited retropropagation of spike bursts from the jejunum to the antrum which was accompanied by emesis. Retropropagation of spike bursts did not occur in one dog who did not exhibit emesis. In addition, abnormal spike bursts occurred frequently, including simultaneously occurring spike bursts in both duodenum and jejunum and nonpropagating short spike bursts in isolated segments of the upper small intestine. As phase III of IDMA disappeared, plasma motilin concentrations remained comparable to those in phase II of normal IDMA but without the cyclic increases. These studies indicate that cisplatin interrupts the regular cycle of IDMA as well as the plasma motilin cycle and produces retropropagation of spike bursts and abnormal spike bursts. These changes in both motility and plasma motilin levels may play a part in the mechanism of emesis induced by cisplatin in dogs.

A phase II trial of homoharringtonine and caracemide in the treatment of patients with advanced large bowel cancer.

Twenty-four previously untreated, ambulatory patients with advanced colorectal carcinoma were treated with either caracemide (11 patients) or homoharringtonine (13 patients). No objective responses were observed in any of the treatment cohorts. Caracemide was well tolerated with the exception of one death due to sepsis. On the homoharringtonine arm one patient died of pulmonary sepsis, one patient experienced grade 4 leukopenia requiring more than 4 weeks of recovery, and an additional patient developed grade 4 renal failure. These severe and unexpected complications caused early termination of accrual to the homoharringtonine arm of the study. These agents have no activity in the treatment of advanced colorectal carcinoma.