Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study.

BACKGROUND: Platinum-resistant ovarian cancer (PROC) constitutes a therapeutic dilemma with limited efficacy from traditional cytotoxic agents. Based on prior data suggesting that scheduling alterations of platinum would increase activity, the aim of the present study was to assess the potential therapeutic benefit of phenoxodiol (PXD), a novel biomodulator shown to have chemoresistance reversing potential, when combined with weekly AUC2-carboplatin in PROC patients. PATIENTS AND METHODS: A multicenter randomized double-blind placebo controlled phase-III-study was conducted to compare oral PXD plus AUC2-carboplatin (group 1) versus placebo plus AUC2-carboplatin (group 2) weekly in PROC patients. The primary end point was progression-free-survival (PFS). Secondary objectives included overall survival (OS), response rates, duration of response and quality of life. RESULTS: The study was terminated early 14 April 2009, after recruitment of 142 patients due to feasibility and recruitment challenges. A total of 142 patients were randomized. The groups were well balanced in terms of important baseline characteristics. The median PFS for group 1 was 15.4 weeks [95% confidence interval (CI) 11.1-21.0] versus 20.1 weeks for group 2 (95% CI = 13.1-33.4); P = 0.3. The objective response rate and median survival in group 1 versus group 2 was 0% versus 1% and 38.3 weeks (95% CI 32.0-45.3) versus 45.7 weeks (95% CI 35.6-58.0), respectively. PXD appeared to be well tolerated. The main reason for dose modification in both groups was hematologic toxicity. CONCLUSIONS: Orally delivered PXD showed no evidence of clinical activity, when combined with weekly AUC2-carboplatin in PROC. In addition, single-agent weekly AUC2-carboplatin appeared to be inactive by response criteria in a homogenously defined population of PROC. This has implications for the design of future studies.

First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cancer of the cervix--a phase II study.

OBJECTIVE: The aim of this study was to assess the role of first-line chemotherapy with paclitaxel and platinum in the treatment of advanced or recurrent cervix cancer. METHODS: Twenty patients with advanced or recurrent cancer of the cervix with no prior chemotherapy and measurable disease were entered in a phase II trial from September 1995 to September 1998. Seventeen patients were treated with paclitaxel at 135 mg/m(2) over 24 h followed by cisplatin at 75 mg/m(2) every 4 weeks. Three patients with impaired renal function were treated with paclitaxel at 135 mg/m(2) over 3 h with carboplatin at 300 mg/m(2). RESULTS: A clinical response rate of 45% was noted (two complete responses and seven partial responses) with a median duration of 6 months (range: 1.5-9). The median progression-free interval and overall survival in patients with a clinical response was 10.5 and 13 months, respectively, compared to 4 (P = 0.015) and 6 months in the nonresponders (P = 0. 14). Seven of nine patients (77.8%) with a clinical response are alive. Patients with recurrences outside the radiation field had twice the response rate (60%) than that of those within the radiated field. The chemotherapy was well tolerated; the most significant toxicity was grade 3/4 neutropenia (55%). No patient had discontinuation of chemotherapy due to toxicity. CONCLUSIONS: First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cervix cancer is promising and deserves consideration for large phase III trials.

Role of salvage chemotherapy with topotecan and cisplatin in patients with paclitaxel- and platinum-resistant recurrent ovarian or primary peritoneal cancer: a phase II pilot study.

BACKGROUND AND OBJECTIVES: We assessed the role of salvage chemotherapy with topotecan and cisplatin in patients with platinum- and paclitaxel-resistant advanced and recurrent ovarian or primary peritoneal cancer, based on the reported in vivo and in vitro synergism between these two drugs. METHODS: Twenty patients were entered in this phase II trial from November 1997 to November 1998. They received cisplatin at 50 mg/m(2) on day 1 with topotecan at 0.6 mg/m(2) from day 1 to 5 every 28 days. In 70% of patients (14/20), this combination represented at least a third line of therapy. RESULTS: A clinical response rate of 13.3% (two partial responses) was obtained in the 15 patients with evaluable disease. Sixty percent of patients (9/15) had stable disease and 26.7% (4/15) had progression. The median progression-free interval and survival were 4 months and 7 months, respectively. The 20 patients evaluable for toxicity received a mean of four chemotherapy cycles. Dose reductions were required in 45% of patients despite the administration of growth factors. The major dose-limiting toxicity was a 50% occurrence (10/20) of grade 4 thrombocytopenia and 30% (6/20) grade 4 neutropenia. There was one septic death. CONCLUSIONS: These data suggest that combination therapy with topotecan and cisplatin has minimal activity in platinum- and paclitaxel-resistant advanced and recurrent ovarian or primary peritoneal cancer at the doses utilized in this trial.

Adenocarcinoma of the ileum with an enterotubal fistula presenting as an adnexal mass.

Small bowel adenocarcinomas account for 3% of gastrointestinal malignancies, and 20 to 25% of these arise in the ileum. Clinical presentation is variable, and early diagnosis is difficult. A 56-year-old postmenopausal woman presented with crampy abdominal pain, anorexia, and weight loss. Pelvic examination and ultrasound revealed a 6 x 8-cm complex right adnexal mass. At laparotomy, en bloc resection of the right adnexa and the densely adherent ileal segment was performed along with a hysterectomy and a left salpingo-oophorectomy. The final pathology showed a moderately differentiated invasive adenocarcinoma of the ileum with a malignant enterotubal fistula. This is the first case reported in the literature of an ileal adenocarcinoma with a tubal fistula masquerading as an adnexal mass.

High levels of CA-125 in a case of a parasitic leiomyoma presenting as an abdominal mass.

A 32-year-old woman presented with increasing abdominal girth and discomfort secondary to a 18-week-size mass and a CA-125 level of 1539. She underwent an exploratory laparotomy and resection of a parasitic fibroid following which the CA-125 levels decreased and normalized within a month. A review of English literature indicates that association of raised CA-125 levels with fibroids is inconsistent and very modest and such high levels have not been previously reported.

Mucinous adenocarcinomas of the vulva.

An 80-year-old nullipara had a 2.0-cm cystic tumor of the right labium majus. Histologic diagnosis was mucinous eccrine carcinoma. Seventy-five percent of these rare skin adnexal tumors arise on the face, eyelid, or scalp; but none has been reported on the vulva. Indolent localized growth is usual with regional nodal spread in 11% and distant metastases in 3%. A 67-year-old multipara had a 1.2-cm polypoidal nodule of the posterior fourchette. Histologically, a colonic type mucinous carcinoma was arising within a villous adenoma. Mucicarmine and CEA stains were positive. Extensive workup failed to reveal other primary cancers in either patient. Both patients are well 19 and 17 months after radical vulvectomies and node-negative groin dissections. These cases illustrate further the diversity in cell type and biologic behavior of vulvar adenocarcinomas.