Phase II trial of piperazinedione in patients with advanced or recurrent uterine sarcoma. A Gynecologic Oncology Group study

Twenty patients with advanced or recurrent uterine sarcoma no longer amenable to control with surgery and/or radiotherapy were entered into study by Gynecologic Oncology Group institutions to receive piperazinedione 9 mg/m2 intravenously every 3 weeks. One patient was deemed to be ineligible for study. Among the 19 evaluable patients, only one response was observed, a partial response in a patient with leiomyosarcoma. Adverse effects consisted primarily of myelosuppression and were tolerable. Piperazinedione at the dose and schedule tested appears to have little activity against uterine sarcomas.     

Evaluation of azotemic patients: diagnostic yield of initial US examination

To determine whether renal ultrasound (US) is necessary in all patients with azotemia, the authors retrospectively evaluated renal US examinations in 394 azotemic patients. The patients included 119 patients considered clinically to be at high risk for postrenal urinary obstruction and 275 patients considered to be at low risk. In the high-risk population, 35 patients were found to have hydronephrosis (29%). In the low-risk population, three patients were found to have hydronephrosis (1%). In two of these patients surgical intervention resulted in reversal of the azotemia. The authors recommend that renal US be performed in all high-risk patients and in low-risk patients only if temporization and standard medical treatment do not resolve the azotemia.     

Retiform differentiation in ovarian Sertoli-Leydig cell tumors. A clinicopathologic study of six cases from a Gynecologic Oncology Group study

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.     

A phase II trial of diaziquone (AZQ) in mixed mesodermal sarcomas of the uterus

Summary 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 reponse 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. Address for offprints: GOG Administrative Office, Suite 1945, 1234 Market Street, Philadelphia, PA 19107, USA     

Phase II trials of cisplatin and piperazinedione as single agents in the treatment of advanced or recurrent non-squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study

A total of 42 patients with advanced or recurrent carcinoma of the cervix, other than squamous cell carcinoma, were entered onto two phase II studies by the Gynecologic Oncology Group. Of 16 patients registered to receive piperazinedione at a dose of 9 mg/m2 iv every 3 weeks, two were inevaluable for response because of the lack of measurable disease. Of the remaining 14, two (14%) had complete response. Adverse effects were limited to myelosuppression, nausea and vomiting, and nephrotoxicity. Among 26 patients registered to receive cisplatin, three were deemed ineligible and three were inevaluable for the study. Of the remaining 20 patients, one (5%) had complete response and three (15%) had partial response. Primary adverse effects included myelosuppression, frequent nausea and vomiting, and nephrotoxicity. The most common histologic subtypes noted were adenocarcinoma and adenosquamous carcinoma, and responses were noted among patients with each subtype on each drug. Both drugs appear to possess moderate activity against non-squamous carcinoma of the cervix.     

The prognostic significance of basic fibroblast growth factor in cutaneous malignant melanoma

Basic fibroblast growth factor (bFGF) is a growth factor and an angiogenesis factor which may play a role in the evolution of cutaneous malignant melanoma (CMM). In this study, we evaluated the distribution of bFGF in CMM using immunochemical methods and correlated the pattern of bFGF expression with the clinical course. Formalin-fixed, paraffin-embedded sections of 46 CMMs were immunostained with a high-affinity purified antibody raised against human bFGF. CMM were categorized into lesions that exhibited subsequent recurrence (local, regional and/or systemic) or recurrence-free lesions. The minimum follow-up time was 5 years. Expression of bFGF within the tumors and in peritumoral and intratumoral blood vessels was similar in the two groups. Comparable results were attained when 8 recurring vs 8 non-recurring CMM, selected from the above tumors, were matched for age, gender, anatomic site and tumor thickness. These results suggest that the biologic behavior of CMM may not be predicted by immunoreactivity to bFGF in CMM cells or in the local tumor vasculature.     

Phase II trial of acivivin in patients with advanced epithelial ovarian carcinoma

Summary Twenty-four evaluable patients with epithelial ovarian cancer resistant to primary therapy, or relapsing after response to initial therapy, were treated with acivicin utilizing a daily \xs 5 schedule. One patient achieved a partial response lasting five months; the remaining 23 patients showed no objective response. Profound and dose-limiting neurological toxicity was seen in 11 patients. Acivicin is inactive in patients with previously treated ovarian cancer and has a poor therapeutic index due to neurologic adverse effects in this patient population. The profound neurotoxicity may be related to prior therapy with cisplatin, to protein binding in ascitic fluid accumulations or to yet undefined parameters.     

Characteristics of caudal ventrolateral medullary neurons antidromically activated from rostral ventrolateral medulla in the rabbit.

We made extracellular recordings from 107 spontaneously active neurons in the caudal ventrolateral medulla, after identifying the cells by antidromically activating them from the rostral ventrolateral medulla, in urethane-anesthetized rabbits. We tested the response of these neurons to inputs from baroreceptors and chemoreceptors. The median conduction velocity for antidromically activated neurons was 0.84 m/s. Raising blood pressure with intravenous noradrenaline excited 22% of 96 neurons tested, inhibited 61%, and had no effect on the remaining 17%. The spontaneous discharge rate of neurons excited by an increase in blood pressure was 1.6 +/- 0.3 spikes/s, lower than the discharge rate of neurons inhibited by this procedure (4.9 +/- 0.5 spikes/s). Excitation of chemoreceptors by hypoxia increased the discharge rate of 14/16 neurons tested in the group excited by baroreceptor inputs. In the group inhibited by baroreceptor inputs 21/35 neurons tested were excited and 12/35 neurons were inhibited by chemoreceptor inputs. Neurons excited by an increase in blood pressure were located in the previously defined caudal vasodepressor region and in a region just rostral to the obex, intermediate between the vasodepressor region and the rostral sympathoexcitatory region. These neurons may form part of the central inhibitory link in the baroreceptor-vasomotor pathway. Other antidromically activated neurons in the vasodepressor region may be inhibitory vasomotor cells with a function relatively independent of baroreceptor inputs, or they may be A1 catecholamine neurons, with axons passing through the rostral medulla en route to the forebrain.     

Surgical aspects of subungual malignant melanomas. The Scottish Melanoma Group.

The incidence, treatment, and survival of subungual malignant melanomas in Scotland is reviewed from the Scottish Melanoma Group database. Between 1979 and 1989, 100 cases of subungual melanoma were identified (2.8% of all malignant melanomas in Scotland). The tumors tended to be locally advanced at the time of presentation (mean Breslow depth, 4.7 mm +/- 3.0 mm), and this is reflected in an overall 5-year survival of 41%. There was no difference in the survival of patients treated with local/proximal interphalangeal (PIP) joint amputation compared with those having more proximal amputations. Because nearly 70% of these tumors arose on the thumb or hallux, it is concluded that, provided adequate clearance could be obtained, less radical excision should be performed for these lesions to maintain maximum function.