Identification of risk factors for requiring transfusion during front-line chemotherapy for ovarian cancer.

OBJECTIVE: Anemia requiring red blood cell (RBC) transfusion is common in ovarian cancer (OC) patients receiving post-debulking surgery chemotherapy. Erythropoietin use has been shown to decrease transfusion requirements in patients receiving chemotherapy. We sought to identify pretreatment risk factors that could identify patients at increased risk for requiring RBC transfusion during first-line treatment for ovarian cancer. METHODS: One hundred seventy-five consecutive patients who received chemotherapy with either carboplatin-paclitaxel or cisplatin-paclitaxel following debulking surgery for epithelial OC from 1993 to 1996 were identified. No patient received erythropoietin. Patient characteristics recorded included: age, stage, prechemotherapy hemoglobin, nadir hemoglobin, number of cycles and doses of chemotherapy received. The outcome was requiring RBC transfusion. Independent predictors of requiring RBC transfusion were identified using multivariate analyses. RESULTS: Median age of the cohort was 62 years (range, 28-86). Seventy-one and four-tenths percent had FIGO stage III/IV disease. Median prechemotherapy hemoglobin was 11 g/dL (range, 7.1-15.4); median nadir hemoglobin was 9.3 g/dL (range, 6.6-11.1). One hundred nineteen (66%) patients received cisplatin-paclitaxel, and 61 (34%) received carboplatin-paclitaxel. Of 175 patients, 31 (18%, 95% CI = 12-23%) required RBC transfusion. Independent risk factors for RBC transfusion were prechemotherapy hemoglobin <10 g/dL (P < 0.01, odds ratio = 3.78, 95% CI = 1.52-9.44) and carboplatin-paclitaxel versus cisplatin-paclitaxel treatment (P = 0.01, odds ratio = 3.14, 95% CI = 1.27-7.76). Of 175 patients, 40 (22.8%) had a prechemotherapy hemoglobin <10 g/dL. Fifty percent of patients with prechemotherapy hemoglobin <10 g/dL who received carboplatin-paclitaxel required RBC transfusion, compared with 7.7% of patients with hemoglobin >10 g/dL who received cisplatin-paclitaxel. CONCLUSION: Ovarian cancer patients frequently require RBC transfusion during postdebulking platinum-paclitaxel chemotherapy. Patients with prechemotherapy hemoglobin <10 g/dL and those receiving carboplatin-paclitaxel are at increased risk of requiring RBC transfusion. Early initiation of erythropoietin use in such patients may reduce transfusion needs.

Primary intravenous paclitaxel and platinum chemotherapy for high-risk Stage I epithelial ovarian carcinoma.

OBJECTIVE: To evaluate the efficacy of intravenous (i.v.) paclitaxel and platinum chemotherapy in patients with high-risk Stage I epithelial ovarian carcinoma. METHODS: We performed a retrospective chart review of all patients with Stage I ovarian cancer treated at our institution between March 1993 and June 1995. RESULTS: Twenty patients received adjuvant paclitaxel-containing chemotherapy for Stage I ovarian carcinoma after comprehensive surgical staging. Five patients (25%) had Stage IA disease and 15 patients (75%) had Stage IC disease. Tumor grades were: 1, five patients (25%); 2, nine patients (45%); and 3, six patients (30%). Histologic cell types were: clear-cell, ten (50%); endometrioid, five (25%); mucinous, three (15%); and serous, two (10%). Nineteen patients (95%) were treated with i.v. paclitaxel and platinum chemotherapy. One patient (5%) received i.v. paclitaxel alone. Eighteen patients (90%) had five cycles of chemotherapy, while two patients (10%) had three. The 96 total cycles were associated with nine episodes (9%) of significant toxicity: fever, four (4%); severe nausea and vomiting, two (2%); Clostridium difficile enteritis, one (1%); congestive heart failure, one (1%); and anemia, requiring blood transfusion, one (1%). With a median follow-up of 36 months (range 24-50 mos), all 20 patients are alive, and 19 (95%) are disease-free. The one patient (5%) treated with i.v.++paclitaxel alone developed an abdominal recurrence 22 months after diagnosis. CONCLUSION: Primary i.v.++paclitaxel and platinum chemotherapy in patients with high-risk Stage I epithelial ovarian carcinoma is reasonably well tolerated and may improve survival. Larger studies with long-term follow-up are needed.

Phase II trial of paclitaxel in patients with soft-tissue sarcoma.

The response rate (RR) to single-agent chemotherapy with doxorubicin or ifosfamide in patients with advanced soft-tissue sarcoma (STS) is in the range of 20%. Paclitaxel is clinically useful in treating several solid tumors and has demonstrated activity in a series of human sarcoma cell lines. Twenty-eight patients with measurable advanced STS participated in this phase II trial of paclitaxel at 250 mg/m2 administered as a 3-hr i.v. infusion once every 3 weeks. All patients received granulocyte colony-stimulating factor (G-CSF) beginning on the day after paclitaxel and lasting until recovery from neutropenia. No prior chemotherapy had been used in 17 patients; 10 patients had had prior doxorubicin-based therapy; and 1 patient had had intraperitoneal therapy with edatrexate. Two partial responses (PRs) (7%; 95% confidence interval [CI] = 1-23%) were observed. The responding patients included a patient with angiosarcoma of the scalp who had complete regression of cutaneous lesions and improvement of nonmeasurable pulmonary disease lasting 6 months. The other PR occurred in a woman with metastatic uterine leiomyosarcoma and lasted 9 months. Seven patients had stable disease for 3-4 months. Median time to progression for all patients was 3.5 months (range: 2.5-9 months). The mean nadir in the white-blood-cell (WBC) count was 3.8 x 10(3)/microliter (range: [0.2-16.2] x 10(3)/microliter), with a mean nadir in the absolute neutrophil count (ANC) of 2.4 x 10(3)/microliter (range: [0.0-7.1] x 10(3)/microliter). Three patients died while in the study. Two patients with angiosarcoma of the scalp who did not qualify for this study were treated with paclitaxel off protocol, and experienced dramatic tumor regression. The overall response to paclitaxel observed in this heterogeneous group of patients was disappointing. However, the activity seen in angiosarcoma of the scalp suggests that further evaluation is warranted in patients with STS.

Phase II study of "dose-dense" high-dose chemotherapy treatment with peripheral-blood progenitor-cell support as primary treatment for patients with advanced ovarian cancer.

PURPOSE: We performed a pilot phase II study to evaluate the potential for delivery of rapidly sequenced high-dose chemotherapy treatments rescued with autologous peripheral-blood progenitor cells (PBP) in patients with previously untreated, advanced ovarian cancer. PATIENTS AND METHODS: A single cycle of mobilization was used, primed with cyclophosphamide (CPA)/paclitaxel (Txl) and filgrastim (granulocyte colony-stimulating factor [G-CSF]), followed by three cycles of high-dose carboplatin (CBDCA)/Txl and one cycle of high-dose melphalan (MEL), each rescued by PBP. We then analyzed the outcome for a total of 56 consecutive patients treated with high-dose chemotherapy as part of this program. RESULTS: In the phase II pilot, 21 patients were enrolled. There were no treatment-related deaths through 98 high-dose treatments, although 34 treatments were complicated by hospitalization, primarily for neutropenic fever. Seventy-six percent of patients experienced grade 3 to 4 gastrointestinal toxicity and 62% experienced grade 2 to 3 neuropathy. Five of 15 (33%) patients who underwent second-look surgery attained a pathologic complete response. In the overall analysis, 56 patients were reviewed. Forty-four patients were assessable for response by second-look surgery or clinical progression. Fifteen of 44 patients achieved a pathologic complete response (34%). The pathologic complete response rate in optimal-disease patients was 12 of 22 (55%), while only three of 22 (13%) suboptimal stage III and IV patients achieved a pathologic complete response. CONCLUSION: The Gynecologic Oncology Group has initiated a pilot phase II trial of this approach in patients with optimally debulked stage III ovarian cancer. There is no evidence to support the use of this or other aggressive regimens outside of a clinical trial.