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.

Intraperitoneal cisplatin-based chemotherapy for primary treatment of epithelial ovarian cancer.

INTRODUCTION: This study looks at the feasibility of intraperitoneal cisplatin-based treatment in patients newly diagnosed with ovarian cancer in a community hospital setting and provides long-term follow-up of a cohort of patients. METHODS: Sixteen patients with epithelial ovarian cancer were studied. All patients underwent definitive surgical debulking. Patients were scheduled to be treated with six cycles of intraperitoneal cisplatin and either intravenous cyclophosphamide or intravenous doxorubicin at four week intervals. RESULTS: Fifteen patients were evaluable for response. All patients received at least three cycles of intraperitoneal therapy. All patients had an initial clinical response. Nine of 15 patients underwent second-look laparotomy; five of the nine patients had positive second-looks, none had residual macroscopic disease. Of the remaining six patients, five had clinical complete remissions and four are alive without recurrence. CONCLUSION: High-dose intraperitoneal cisplatin-based with sodium thiosulfate protection is generally well-tolerated and possibly an appropriate alternative first-line therapy for selected patients with epithelial ovarian cancer.

Safety and costs of treating neutropenic fever in an outpatient setting.

PURPOSE: The purpose of this study is to analyze the safety of outpatient treatment for cancer patients with chemotherapy-induced neutropenic fever in a community hospital setting and to compare the costs of outpatient treatment with those of inpatient treatment for such patients. PATIENTS AND METHODS: We reviewed charts and charges for 32 consecutive patients initially treated for neutropenic fever with broad-spectrum antibiotics in the offices of Hematology/Oncology Associates (HOA) at the Bennett Cancer Center in the Stamford Hospital January 1997-June 1998. We also reviewed charts and charges for eight consecutive HOA patients with neutropenic fever who met the criteria for outpatient treatment but were initially hospitalized for other reasons during this period. We compared these two groups with respect to mean nadir absolute neutrophil count (ANC), mean number of days when ANC < 1,000 cells cu mm, and mean number of days of intravenous antibiotic treatment. We compared costs for ambulatory and hospital care of the two groups using Health Care Financing Administration (HCFA) payments in 1998 as a proxy for costs. RESULTS: Of 32 patients with neutropenic fever initially treated in the outpatient setting, only four required hospitalization. No patients in either group died in connection with neutropenic fever. Although outpatients received an average of 3.6 days and inpatients only 2.5 days of antibiotic treatment, outpatient treatment was significantly less costly than inpatient treatment. CONCLUSION: In a community hospital setting most cancer patients with neutropenic fever who meet certain criteria can be safely, effectively, and inexpensively treated as outpatients.

Cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil for the treatment of metastatic non-small cell lung cancer. Limited activity of an aggressive chemotherapy regimen.

We conducted a Phase II study to determine the efficacy of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil in patients with untreated non-small cell lung cancer. Patients were accrued through the Connecticut Oncology Association (COA), an organization composed of community and university oncologists. Thirteen COA oncologists enrolled 30 patients over 12 months and 26 were eligible for the final analysis. Patients received cisplatin 75 mg/m2, doxorubicin 30 mg/m2, mitomycin C 6.5 mg/m2, and 5-fluorouracil 750 mg/m2 on day 1. The treatment was repeated every 4 weeks, with mitomycin C given during the first 3 cycles and then every other cycle. There were 5 (19%) partial responses, lasting 1.3-7.3 months. The median time to progression was 10.3 months (0.3-12.5 months). Median survival was 7.5 months (0.3-34 months). The major toxicities were related to myelosuppression and there was one septic death. This study demonstrates the limited efficacy of an aggressive regimen using "active" agents in patients with advanced non-small cell lung cancer.

Bleomycin, vincristine, mitomycin C, and cis-platinum in gynecologic squamous cell carcinomas: a high incidence of pulmonary toxicity.

Twenty-three patients with gynecologic squamous cell carcinomas (20 cervical, 2 vulvar, 1 ovarian) were treated with bleomycin, vincristine, mitomycin-C, and cis-platinum. Twenty-one patients had prior radiation therapy. Of the 21 evaluable patients, the response rate was 48% with a median duration of 4 months. Toxicity in the 23 patients was high, with the most significant being that of pulmonary toxicity. Eight patients had pulmonary toxicity with 5 of 8 dying a respiratory death while free of disease. Bleomycin is excreted primarily by the kidneys, and its half-life is known to increase in patients with renal insufficiency. Patients with advanced, recurrent cervical cancer who have failed radiation therapy often have underlying renal compromise. Extreme caution should be exercised when administering bleomycin with nephrotoxic chemotherapeutic agents in this setting.

17-beta-estradiol levels in patients with small cell carcinoma of the lung.

Human SCCL cell lines produce 17-beta-estradiol (E2) in all cases that we have studied. In order to determine whether this phenomenon has a clinical counterpart, we analyzed sera from 25 consecutive patients with newly diagnosed, untreated SCCL for E2. We found serum E2 concentrations in all patients to be within the normal range. This discrepancy between cell culture and patient-derived data emphasizes yet another dichotomy between in vivo and in vitro observations.

Bombesin production by human small cell carcinoma of the lung.

A series of continuous cell lines of human small cell carcinoma of the lung (SCCL) have been evaluated for the production of bombesin (BN). In early established cultures BN was detected in the medium of 9 out of 11 cell lines and in 6 out of 7 cell homogenates examined. Levels in the medium were frequently higher in cultures of later passages compared to earlier passages of the same line and low levels developed in the two previously negative cell lines. Plasma concentrations were greater than 80 pmol/l in 2 out of 27 (7%) randomly selected patients with SCCL. A culture (DMS 406) established from the tumor of a patient with the highest plasma level (1240 pmol/l) was the highest producer in vitro. The results indicate that BN, which has been demonstrated immunocytochemically to be present in normal bronchial mucosal cells, is frequently produced by SCCL in vitro but elevated plasma levels are infrequently found in patients with this neoplasm.