Robert D. Hilgers

Cisplatin neuropathy. Clinical, electrophysiologic, morphologic, and toxicologic studies

Ten of 11 patients with ovarian cancer receiving cisplatin developed a distal sensory neuropathy, manifested early by decreased vibratory sensibility in toes and depressed ankle jerks and later by uncomfortable paresthesias. Eleven patients receiving cisplatin, 50 mg/m2 monthly (mean total, 580 mg/m2) were studied prospectively with monthly neurologic examinations and conduction velocity determinations of median, peroneal, and sural nerves. Early signs were decreased vibratory sensibility in toes (mean dose, 417 ± 132 mg/m2 [SD]) and loss of ankle jerks (mean dose, 455 ± 86 mg/m2). With continued therapy, four developed paresthesias. Strength was unaffected. Sural nerve responses abruptly disappeared in six patients (mean dose, 383 ± 103 mg/m2). Other conduction velocities remained normal. Electron microscopy of peripheral nerves from four patients showed axonal degeneration and secondary myelin breakdown. Platinum concentrations in three patients were similar in tumor (3.3 μg/g), sural nerves (3.5 μg/g), and spinal ganglia (3.8 μg/g), but lower in brain (0.17 μg/g). This may explain the cisplatin toxicity of peripheral nerves with relative sparing of the central nervous system.

The Syed-Neblett interstitial template in locally advanced gynecological malignancies

Twenty-eight patients with locally advanced malignancies of the cervix and vagina were treated with a combination of external radiation therapy and afterloading Syed-Neblett iridium template. There were 22 patients with squamous cell cancer and two patients with adenocarcinomas of the cervix. Four patients with squamous cell cancer of the vagina were treated with this method. Only patients with locally advanced disease (cervical lesion greater than 4 cm in diameter) and poor vaginal anatomy were selected for this modality of therapy. In our series the incidence of distant failures of 39% seems to confirm the significance of local volume of disease as a prognostic indicator; despite a local control rate of 59%, only 33% of our patients are alive from 25-51 months. Complications occurred in 12 patients (42%). Six patients (22%) developed severe rectal stricture or rectovaginal fistula necessitating diverting sigmoid colostomy; five patients (18%) developed hemorrhagic proctitis with diarrhea and tenesmus; one patient developed vaginal vault necrosis. Complications occurred 7 to 24 months following therapy. Six of the 12 patients developing complications are dead of disease. On the basis of this study and because of the low cure rate and high incidence of complications, the value of the Syed-Neblett template in locally advanced gynecologic malignancies should be reconsidered.

Psychological effects of vulvectomy

Abstract A survey of post-vulvectomy patients revealed that compared with post-hysterectomy patients, they are more likely to be depressed, to harbor feelings of sexual guilt, and to have encapsulated deficits in reality testing. Some of these problems may be prevented. The patient undergoing vulvectomy should receive detailed information before and after the surgery, and psychosexual counseling should be offered to her and her sexual partner on a long-term basis.

Doxorubicin-cisplatin-vinblastine combination chemotherapy of advanced endometrial carcinoma: A Southwest Oncology Group study

A combination of doxorubicin (30 mg/m2 iv), cisplatin (50 mg/m2 iv), and vinblastine (5 mg/m2 iv) repeated every 3-4 weeks was used to treat 55 patients with advanced stage III or IV or recurrent disease. Of the 42 fully evaluable patients, there were 3 complete responders (7%) and 10 partial responders (24%). Responses were of short duration (median of 8 months, range 3-15 months) and the median survival of all evaluable patients was only 10 months from the start of therapy. Leukopenia was the major toxicity and was at least moderate in two-thirds of patients. We conclude that the addition of cisplatin and vinblastine to doxorubicin does not improve the clinical utility of doxorubicin in patients with advanced endometrial cancer.

Randomized phase III trial of chemoimmunotherapy in patients with previously untreated stages III and IV suboptimal disease ovarian cancer: A Southwest Oncology Group study☆

Abstract Between 1979 and 1984, 98 patients considered to have stage III epithelial type ovarian cancer and optimal surgical resections (i.e.,

Meningeal carcinomatosis from an ovarian primary: A clinicopathologic study

Meningeal carcinomatosis due to primary ovarian carcinoma is an uncommon metastasis that presents difficult problems in diagnosis and management of patients known to have this disease. There is evidence that extended survival due to advances in treatment of ovarian carcinoma has improved our ability to diagnose meningeal carcinomatosis of this tumor more often. Herein the first case of meningeal metastasis of primary ovarian cancer with cytologic and postmortem examination is discussed.

Mitoxantrone in epithelial carcinoma of the ovary: A Southwest Oncology Group study

THIRTY-NINE PATIENTS WITH ADVANCED HEAVILY pretreated epithelial carcinoma of the ovary were treated with mitoxantrone (dihydroxyanthracenedione hydro-chloride). Twenty-five patients were started at a dose of 12 mg/m2 q 21d and 13 patients, with compromised bone marrow, at a dose of 10 mg/m2 q 21d. Two stable responses (6%) occurred in 31 fully evaluable patients. The median duration of survival was 17 weeks. The principal toxicity, hematopoietic (primarily leukopenia), was mild and well tolerated. We conclude that mitoxantrone is a relatively inactive drug in the treatment of epithelial ovarian carcinoma.

Squamous Cell Carcinoma of the Vagina

Squamous cell carcinoma of the vagina is one of the least understood malignant tumors arising from the female genital tract. Vital facts on its clinical and biologic behavior are difficult to collate in a cumulative way. Its intermediate position in the pelvis makes it a difficult site to which to apply conventional methods of treatment without associated morbidity; its rareness precludes developing expertise by no more than a few therapists and allows few the opportunity to test new ideas encased in research protocols; and its variegated presentations invite individualization as the only therapeutic approach. Squamous cell carcinoma of the vagina remains an enigma among gynecologic neoplasms.

m-AMSA in epithelial carcinoma of the ovary. A Southwest Oncology Group study

TWENTY-THREE PATIENTS WITH ADVANCED heavily pretreated epithelial carcinoma of the ovary were treated with m-AMSA. Eleven patients received a mean of 2.3 courses at a dose of 40 mg/m2 ± 3 days q 21 days and 12 patients received a mean of 4.3 courses at a dose of 30 mg/m2 ± 3 days q 21 days intravenously. One (5%) partial response in 22 fully evaluable patients was observed. Toxicity was mild and well tolerated. We conclude that m-AMSA is a relatively inactive drug in the treatment of epithelial ovarian carcinoma.

Failure of single dose methotrexate followed by citrovorum factor in nonmetastatic gestational trophoblastic neoplasia.

With increasing cost of medical care, newer methods of administering chemotherapy on an outpatient basis are being sought to reduce the need for hospitalization and protracted losses of valuable time for patients with nonmetastatic gestational trophoblastic neoplasia (NMGTN). To achieve this end, two NMGTN patients were treated with a single course of one dose of methotrexate (MTX) followed by multidose Citrovorum Factor (CF) without observing the expected response. Failure to respond appeared to be due to the schedule of administration. Although the dose and plasma concentrations of MTX were considered to be adequate for cell kill, fractionation--as established by conventional schedules of MTX administration--appeared necessary for response by exposing the maximum number of trophoblastic cells to inhibitory levels of MTX during the S-phase of the cell cycle.