A phase I/II dose escalation study of carboplatin in the treatment of newly diagnosed patients with advanced ovarian cancer receiving paclitaxel.

The objective of this study was to determine the maximum tolerated dose of carboplatin when administered with paclitaxel in previously untreated patients with ovarian cancer. Patients were treated with paclitaxel at 225 mg/m2 for 3 hours followed by carboplatin at an area under the curve (AUC) of 6, 7, 8, or 9 every 3 weeks. Granulocyte colony-stimulating factor was added if needed to maintain dose intensity before dose reductions were used for grade 4 hematologic toxicity or febrile neutropenia. Twenty-two patients were enrolled in the study. At the AUC 6 level, five of six patients finished all six cycles. At the AUC 7 level, four of five patients completed six cycles, although three required dose reductions for toxicity. At the AUC 8 level, all four patients completed six cycles and two required dose reductions. The AUC 9 level was not well tolerated. Only four of seven patients completed six cycles. Neutropenia was common, and transient thrombocytopenia was more severe and required dose reduction, especially in later cycles. An AUC of 8 is the maximum tolerated dose of carboplatin in combination with paclitaxel at 225 mg/m2 for 3 hours.

Relapsing Clostridium difficile toxin-associated colitis in ovarian cancer patients treated with chemotherapy.

Symptomatic relapse of Clostridium difficile toxin-associated colitis occurred in three patients with ovarian cancer. In two patients, C difficile toxin-positive diarrhea initially appeared in association with antibiotic therapy. The third patient developed diarrhea after chemotherapy, without recent antecedent antibiotic administration. Patients were initially treated with oral metronidazole and became asymptomatic and toxin-negative. A symptomatic toxin-positive recurrence then developed after the subsequent course of systemic chemotherapy. Recurrent C difficile toxin-associated colitis or pseudomembranous colitis after chemotherapy has not been reported previously in the gynecologic oncology literature. Clostridium difficile-induced diarrhea must be considered in chemotherapy patients with diarrhea because management concepts vary from those for noninfectious diarrhea.

Gracilis myocutaneous vaginal reconstruction concurrent with total pelvic exenteration.

The gracilis myocutaneous vaginal reconstruction is commonly performed in patients undergoing a total pelvic exenteration. This retrospective review compares the operative and perioperative morbidity in 107 patients who underwent reconstruction with that in 44 patients who did not have reconstruction. With incorporation of the reconstructive procedure, there were no increases in operating time, blood loss, or length of hospitalization. Before 1980, 65% of patients experienced prolapse of the neovagina; in 25% it was severe. The frequency of prolapse has since been decreased to 16% (6% severe) because of several modifications to the initial technique. Modifications have included using smaller flaps, anchoring the neovagina to the levator and retropubic fascia, and, when necessary for mobilization, ligating the neurovascular pedicle. With these modifications, 66% of patients also remained free of wound breakdown or necrosis. The frequency of severe necrosis has decreased from 24% to 13%. The anatomic result of the vaginal reconstructions appears to have been enhanced by these changes in technique.

Use of cisplatin, doxorubicin, and cyclophosphamide to treat advanced and recurrent adenocarcinoma of the endometrium.

Eighteen patients with recurrent or advanced adenocarcinoma of the endometrium were treated with the combination of cisplatin, doxorubicin, and cyclophosphamide between January 1981 and December 1983. Sixteen of the 18 had received prior irradiation. None of the patients had received prior chemotherapy. Fifteen patients had previously received hormones without response. No patients received concurrent hormone treatments. Ten of the 18 patients (56%) achieved an objective response: five (28%) achieved complete response and five (28%) achieved partial response. Myelosuppression was present in seven patients, and two developed neurotoxicity. Combination chemotherapy using cisplatin, doxorubicin, and cyclophosphamide is active in patients with adenocarcinoma of the endometrium, including those who have received prior irradiation and have failed hormonal therapy.

Urinary conduits in gynecologic oncology.

Over an 11-year period (1971 to 1981), 212 urinary conduit surgeries were performed by the Department of Gynecology at the University of Texas, M. D. Anderson Hospital and Tumor Institute at Houston. The urinary diversions were performed as part of the pelvic exenteration operation in 154 patients, for radiation injury in 48 patients, and for palliation of disease recurrence in ten patients. Ninety-three percent had prior pelvic radiotherapy. Various segments of the gastrointestinal tract were used, including the ileum (102), sigmoid colon (99), transverse colon (four), jejunum (four), and others (three). Fifty percent of abnormal preoperative intravenous pyelograms reverted to normal after urinary diversion. Revision of the stoma was required in 6%. Other complications included infection (18%), renal loss (17%), and urinary leaks and fistulae (3%). The overall perioperative mortality was 7%, decreasing from 11% in the first five years to 3% during the last six years. Ureteral stents were routinely used. When selecting a segment of bowel for a urinary conduit, both tissue quality and mobility are important. Mortality and morbidity of urinary conduit surgery continues to decrease with experience.

Endodermal sinus tumor of the vagina and cervix.

This report describes six patients with endodermal sinus tumor of the vagina and cervix, a polypoid friable tumor whose clinical presentation in girls younger than age 3 years simulates the presentation of sarcoma botryoides. In four of the six patients, the referring diagnosis was sarcoma botryoides. Five patients were treated with excisional surgery, and all six with chemotherapy. One patient with pulmonary metastases maintained a complete clinical response to vincristine, actinomycin-D, and cyclophosphamide (VAC) for 11 months. This is the first report of such a response. One patient with a vaginal lesion remains clinically free of disease 2 years after local excision and 18 months of VAC chemotherapy. This is the first report of apparently successful therapy that allowed retention of childbearing potential. Four of the six patients have been disease-free from 2 to 23 years. After examining the world literature, it is concluded that a combination of chemotherapy and surgery offers a reasonable prospect of cure with a minimum of serious side effects.