Results of a prospective dose-intensive regimen in 27 patients with small cell carcinoma of the ovary of the hypercalcemic type.

BACKGROUND: The evaluation of first-line intensive combination therapy in small cell carcinoma of the ovary (SCCO). PATIENTS AND METHODS: Debulking surgery; four to six cycles of chemotherapy with cisplatin (P) 80 mg/m(2) day 1, adriamycin (A) 40 mg/m(2) day 1, vepeside (V) 75 mg/m(2)/day days 1-3, cyclophosphamide (EP) 300 mg/m(2)/day days 1-3, every 3 weeks and granulocyte colony-stimulating factor with, in case of a complete remission, high-dose chemotherapy with carboplatin, vepeside, cyclophosphamide and stem-cell support. RESULTS: Twenty-seven patients (median age 25 years); International Federation of Gynecology and Obstetrics stage: five I, four IIC, 17 IIIC-IV and one unknown. Twenty patients underwent complete surgery. Eight patients progressed under chemotherapy. Among 18 patients in complete response (CR), 10 received high-dose chemotherapy (CT) (three stem-cell collection failures, two protocol violations, two disease progression and one refusal). The main grade 3-4 toxic effects were hematologic. There were eight relapses among the 18 CR, four of which were pelvic alone. Among the 27 patients, 13 died and 10 patients are in CR1, three in CR2. The median follow-up is 37 months (8-166) and the median duration of the 18 CR is 30 months (5-111). Overall survival at 1 and 3 years is 58% [confidence interval (CI) 40% to 75%] and 49% (CI 30% to 67%). CONCLUSIONS: Initial dose-intensive therapy achieves interesting overall survival in SCCO.

Efficacy and safety of single agent capecitabine in pretreated metastatic breast cancer patients from the French compassionate use program.

BACKGROUND: A retrospective source review identifying predictive factors and assessing safety and efficacy in pretreated metastatic breast cancer (MBC) patients treated with capecitabine in a French compassionate-use program. PATIENTS AND METHODS: 197 patients received capecitabine at an initial total dose 0.25-3.0 g/m2/day, twice daily for 14 consecutive days, every 3 weeks. RESULTS: Median patient age was 56 years (range, 31-88), 19% had performance status (PS) 3-4. Prior palliative and adjuvant treatment was reported in 96 and 61% of patients respectively. Best overall response rate (ORR) was 15% (95% confidence interval [CI], 11-21%) and 49% had benefit (CR, PR or SD). Median time to progression (TTP) and overall survival were 4.8 and 14.7 months, respectively. Median TTP in responders was 8.9 months (95%CI 6.1-11.7). Grade 3/4 neutropenia and grade 3 thrombocytopenia occurred in 8 and 3% of patients respectively. Hand-foot syndrome (grade 3/4 in 16% of patients), diarrhea, stomatitis and asthenia were prevalent. Multivariate analysis showed ORR was significantly influenced by PS > or = 2 (p = 0.004), time from metastases diagnosis to capecitabine treatment (p = 0.015) and presence of liver metastases at inclusion (p = 0.047). Abnormal liver function tests at baseline were associated with severe thrombocytopenia and anemia. Four treatment-related deaths occurred. CONCLUSION: Capecitabine is active in heavily pretreated MBC patients and has a favorable toxicity profile with the added advantage of being an oral drug administered in an outpatient setting.

The integration of anthracyclines in the treatment of advanced ovarian cancer.

Since the publication of the Gynecologic Oncology Group (GOG) protocol 111 in 1996, and the results of the Arbeitgemeinschaft Gyna kologische Onkologie (AGO) trial Ovar-3 and the GOG protocol 158, the combination of platinum and paclitaxel has been adopted as the standard therapy in advanced ovarian cancer. One option for achieving further progress in the first-line treatment of advanced ovarian cancer might be the addition of noncross-resistant drugs to the two-drug regimen. Meta-analysis showed a survival benefit for platinum-anthracycline based combinations as compared to platinum-based combinations without anthracyclines. An AGO phase I/II trial compared epirubicin in combination with carboplatin and paclitaxel in untreated patients with gynecological malignancies. Based on the results of this study a randomized phase III trial together with the French GINECO group was conducted. The trial started 11/97 and was closed 11/99. All 1281 patients were randomized. Currently, 1132 end-of-therapy reports have been issued. Nine hundred eighty nine (87%) patients completed six cycles of treatment. Treatment and toxicity data are available for these patients. Three hundred thirty five patients had a measurable residual tumor after initial debulking surgery. Response data of 228 patients (111 ET-Carbo, 117 Carbo-T) are available.

Prognostic factors in ovarian carcinoma in complete histologic remission at second-look surgery.

Prognosis of ovarian carcinoma in complete histologic remission (CHR) at second-look surgery is still controversial. In a series of 83 patients in CHR we studied retrospectively several prognostic factors (age, stage, histologic grade, histologic type, initial residual disease after surgery, CA 125 normalization period) to determine which patients present a high risk of relapsing after CHR and could be included in therapeutic protocols for consolidation treatment. Univariate analysis showed that the combination of CA 125 normalization < 8 weeks with absence of macroscopic tumoral residue after initial surgery permits the definition of a group with a very good prognosis, while for patients with CA 125 normalization period > 8 weeks and an initial macroscopic residual tumor, the prognosis is relatively poor (progression-free survival 100% vs. 47%, at 2 years P < 0.05). Using the Cox multivariate analysis, only the initial tumoral residue is of prognostic significance for progression-free survival; there is no prognostic significance for overall survival. The therapeutic strategy for ovarian cancer may be improved for patients in CHR after second-look surgery by determining those at high risk, making it possible to confine consolidation treatment trials to such a group.

Intraperitoneal mitoxantrone as consolidation treatment for patients with ovarian carcinoma in pathologic complete remission.

BACKGROUND: Stages II-IV ovarian cancer in pathologic complete remission (pCR) at second-look surgery have a high relapse rate (50%) during the first 2 years. Considering relapse sites (abdomen and/or pelvis), intraperitoneal (IP) therapy is a logical approach. Mitoxantrone is an effective drug against ovarian cancer cells in vitro and is an attractive agent for IP therapy because of its very low peritoneal clearance. The value of IP mitoxantrone was studied as consolidation treatment of ovarian cancer in pCR at second-look surgery. METHODS: Fifty patients with Stages II-IV ovarian cancer (8, Stage II; 37, Stage III; 5, Stage IV) were included in this Phase II study, which began in June 1988. All patients had undergone initial cytoreductive surgery followed by 6 cyclophosphamide, doxorubicin, and cisplatin cycles. All patients were in pCR, as confirmed by second-look surgery. Consolidation treatment consists of 20 mg (total dose per cycle) IP mitoxantrone every 3 weeks for six cycles. RESULTS: Toxicity was limited to mild abdominal pain not requiring dose reduction (90% pain grade < or = 2). With a median follow-up of 2 years, the 5-year predicted survival is 59.8% (95% confidence interval [CI], 48.3 - 71.3), and the disease-free survival (DFS) rate is 47.3% (95% CI, 36.7 - 57.9). Patients with no or microscopic residual disease after initial surgery had a better 5-year DFS rate (75.8%) than those with macroscopic residual disease (31.2%) (P = 0.01). CONCLUSION: IP mitoxantrone (20 mg/cycle) is feasible with an acceptable abdominal toxicity. The results in terms of DFS are encouraging, but a randomized study versus no treatment is necessary to prove the value of this consolidation treatment.

Intraperitoneal mitoxantrone as consolidation treatment for stage III ovarian carcinoma: a pilot study.

In June 1986 we initiated an intra-peritoneal (IP) mitoxantrone chemotherapy trial as consolidation treatment for ovarian carcinoma in CR or PR after induction therapy (surgery + CHAP combination chemotherapy). Thirty-two patients received 25 mg IP mitoxantrone every 3 wk for 6 months. The most frequent side-effects were abdominal pains; haematological toxicity was minimal. The response was assessed by third-look surgery. In group I patients (patients in histological complete remission at second-look surgery) 12 of 14 evaluable patients remained in CR at the time of third look. Ten of the 12 patients are still alive with no evidence of disease (NED) with a median follow-up of 9.7 months after completion of treatment. In group II patients (microscopic residual disease at second-look surgery), 7 of 9 evaluable patients entered in CR at the time of third look; 6 of the 7 are still alive with NED and with a median follow-up of 14.3 months. In 7 group III patients (macroscopic residual disease at the time of second look) no response to IP therapy was observed and all patients progressed. We conclude that IP mitoxantrone is a valuable consolidation treatment for patients in CR or with minimal residual disease; further follow-up is necessary to assess the impact on duration of remission and survival.

High dose intravenous IgG followed by splenectomy versus splenectomy alone in idiopathic thrombocytopenic purpura refractory to steroids.

A total of twenty-six patients with idiopathic thrombocytopenic purpura ITP refractory to corticosteroids were alternately allocated to undergo splenectomy alone (N = 12) or to receive a 5 day course of high dose immunoglobulin G i.v. immediately followed by splenectomy (N = 14). Although there were less initial failures after splenectomy in patients receiving IgG, the proportion of sustained complete remission at 1 and 2 years was identical in both groups. It is concluded that high dose IgG infusions do not improve the results of splenectomy in refractory ITP.

[Acute myeloblastic leukemias and myelodysplasias: treatment with low doses of aracytine]. / Leucémies aiguës myéloblastiques et myélodysplasies: traitement par aracytine à faible dose.

The anti-leukaemic effect of low-dose cytosine arabinoside was assessed in 36 patients; 15 patients presented with an acute myeloblastic leukaemia and were treated in first induction because of age or preexisting disease and clinical and biological stabilization was obtained in 7 cases, with a mean duration of 8.7 months. In 4 relapsed patients 2 complete remissions were obtained, 1 of which after several courses of cytosine arabinoside. In all cases an important haematopoietic and extra-haematopoietic toxicity was noticed. In 15 patients treated for a myelodysplastic syndrome terminating in acute myeloblastic leukaemia stabilization was obtained in 8 cases, but final conclusions were difficult. The cytotoxic effect of cytosine arabinoside even at low dosage remains important. The optimal modalities in the administration, and the actual advantages of this treatment compared with conventional chemotherapy have still to be defined.