Gary A. Johnson

Randomized phase 3 trial of interferon gamma-1b plus standard carboplatin/paclitaxel versus carboplatin/paclitaxel alone for first-line treatment of advanced ovarian and primary peritoneal carcinomas: Results from a prospectively designed analysis of progression-free survival

OBJECTIVES Interferon gamma (IFN-gamma) is a pleiotropic cytokine with antiproliferative, immunostimulatory, and chemosensitization properties. This trial was designed to evaluate IFN-gamma 1b plus carboplatin and paclitaxel in treatment-naive ovarian cancer (OC) and primary peritoneal carcinoma (PPC) patients. METHODS Eligible patients were randomized to 6 cycles of carboplatin/paclitaxel every 3 weeks or the same in combination with IFN-gamma 1b (100 microg 3x/wk subcutaneously). The primary endpoint was overall survival (OS) time (target hazard ratio (HR)=0.77). Secondary endpoints included progression-free survival (target HR=0.7), based on blinded review of serial imaging scans, physical exams, and CA-125 levels. RESULTS 847 patients were enrolled (OC 774, PPC 73) in Europe (n=539) and North/South America (n=308) from January 29, 2002 to March 31, 2004 and stratified according to: optimal debulking (n=271) versus suboptimal debulking with plans for interval debulking (PID) (n=238) or no PID (n=338). The study stopped early following a protocol-defined second interim analysis which revealed significantly shorter OS time in patients receiving IFN-gamma 1b plus chemotherapy compared to chemotherapy alone (1138 days vs. not estimable, HR=1.45, 95% CI=1.15-1.83). At the time of the analysis, 169 of 426 (39.7%) patients in the IFN-gamma 1b plus chemotherapy group had died compared to 128 of 421 (30.4%) in the chemotherapy alone group. Serious adverse events were more common in the IFN-gamma 1b plus chemotherapy group (48.5% vs. 35.4%), primarily due to a higher incidence of serious hematological toxicities (34.5% vs. 22.7%). CONCLUSIONS Treatment with IFN-gamma 1b in combination with carboplatin/paclitaxel does not have a role in the first-line treatment of advanced ovarian cancer.

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 isotretinoin and alpha interferon in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

From January 1993 through January 1996, 37 patients with unresectable squamous carcinoma of the cervix were entered on study and scheduled to receive oral isotretinoin 1 mg/kg per day with subcutaneous alpha interferon 6,000,000 units/day. A course was defined as 4 continuous weeks of therapy. The mean number of four-course cycles delivered was 1.8. One patient was ineligible because of wrong cell type and two were never treated. Thus, 34 patients were evaluable for toxicity. Eight patients were inevaluable for response. Five did not receive a complete 4-week course and three did not have additional tumor measurements; thus 26 were evaluable for response. Prior radiotherapy had been given to 25 patients and prior chemotherapy to 23 patients. There was no grade 4 neutropenia. The incidence of Gynecologic Oncology Group (GOG) grade 3 granulocytopenia and thrombocytopenia was 8.8% and 5.8%, respectively. Six patients (17.6%) developed grade 3 or worse nausea and vomiting. Four (11.7%) patients developed grade 3 neurologic symptoms. There were no complete responses and one partial response. The overall response rate was 3.8% (95% confidence interval, 0.1-19.6%). In this pretreated population, isotretinoin and alpha interferon in the dose and schedule employed exhibit minimal activity.

Laparoscopic paraaortic lymphadenectomy using laparosonic coagulating shears

With marked innovations in endosurgical instrumentation, operative laparoscopy to include lymphadenectomy has become feasible and has a valuable role in the management of gynecologic malignancy. We used laparosonic coagulating shears (LCS) for laparoscopic paraaortic lymphadenectomy in two women with cervical carcinoma. Operating times for the laparoscopic portion were 55 and 65 minutes and blood loss was 20 and 30 ml, respectively. No surgical complications were encountered. Lymphatic tissues were evaluated histologically and no thermal artifacts were identified. The major advantage of the ultrasonically activated scalpel of the LCS is the ability to cut and coagulate tissues simultaneously without electrical current. The LCS may afford the surgeon a greater margin of safety than unipolar electrocoagulation scissors by eliminating potential thermal and electrical injury to vital structures. Ultrasonic-activated technology deserves extended clinical investigation in laparoscopic lymphadenectomy to substantiate our preliminary findings, as well as to explore its potential in gynecologic oncology.