DOCETAXEL AND CARBOPLATIN AT AUC-7 AS FIRST-LINE CHEMOTHERAPY IN ADVANCED EPITHELIAL OVARIAN CANCER: A NON-RANDOMIZED CLINICAL TRIAL

M. Salimi MD , M. Davaee MD

Iranian Cancer Institute, Tehran, Iran

  • Abstract

    Twenty-eight patients referred to the Iranian Cancer Institute were studied. All were diagnosed to have stage 3 or 4 epithelial ovarian cancer and had undergone total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. After 6 cycles of chemotherapy, using Docetaxel at 75 mg/m2 followed by Carboplatin at AUC-7, both given intravenously every 3 weeks, the following results were obtained: complete remission: 10/28 (35%), partial remission: 16/28 (57%), stable disease: 2/28 (7%). Second look laparotomy was performed in all 10 patients with complete remission and complete pathologic remission was found in 4(40%) cases. We conclude that Docetaxel/Carboplatin regimen at the above doses and schedule is highly active in this setting and needs to be compared in a phase 3 trial with standard Paclitaxel-based regimens.

    Keywords · Docetaxel · Carboplatin · epithelial ovarian cancer

    • Introduction

    Docetaxel is a spindle poison with a mechanism of action different from Vinca alkaloids. It enhances micro-tubule assembly and inhibits depolymeri-zation.1 Pre-clinically and clinically, Docetaxel has shown a great range of ani-tumor activity, and evidence exists that Docetaxel has activity in Paclitaxel resistant cell lines.2 As it has produced consistent anti-tumor response in ovarian cancer patients in phase-1 trials, this trial was conducted to evaluate the drug efficacy and its toxic effects.

    Materials and Methods

    This open, non-randomized and prospective clinical trial was conducted from February 1996 to December 1997, on 28 Iranian patients who had been referred to the Iranian Cancer Institute. All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentec-tomy with optimal debulking prior to their referral.

    Docetaxel was given intravenously (in the form of a one-hour infusion) and at a dose of 75 mg/m2 followed by Carboplatin at AUC-7. Mean age was 50 years. Eighteen patients (64%) had stage 3 and 10 patients (35%) had stage 4 epithelial ovarian cancer. After 6 cycles of chemotherapy, clinical response was evaluated and second look laparotomy was performed in all 10 patients who had achieved a clinical complete remission (normal image and CA-125 level).

    Results

    Radiological methods and serum CA-125 levels assessed the clinical response. Treatment results are summarized in Table1. One patient was found to have unresectable disease at second-look laparotomy.

    Toxicity: Grade 3 neutropenia was observed in 2(7%) patients, grade 3 thrombocytopenia in 2(7%), and grade 4 non-hematologic toxicity in none of them. Grade 3 mucositis was observed in 1 (3.5%) patient, grade 2 neurotoxicity in 10 (35%), and grade 3 neurotoxicity in 2 (7%) patients. No grade 4 non-hematologic toxicity was observed in this study.

    Discussion

    The first Taxane, Paclitaxel has been comprehensively reviewed and its clinical efficacy in epithelial ovarian cancer is generally established.3 Docetaxel is the second Taxane to reach the clinic and has certain properties which distinguishes it from Paclitaxel notably in regard to differences in potency, tubulin binding, cellular pharmacology and normal tissue toxicity. 2 Randomized trials in breast cancer patients have indicated the superiority of Docetaxel over Doxorubicin, though the same was not reported for Paclitaxel in a separate study. Thus, it is conceivable that Docetaxel may be more effective than Paclitaxel in ovarian cancer.

    Moreover it may have an advantage in causing less neurotoxicity, particularly in combination with a platinum compound. 2,4

    In phase-2 trials on ovarian cancer, Docetaxel had a pooled response rate of 29% (in 155 patients with platinum-refractory disease) and the median response duration was 7 months. These results were comparable with those obtained with Paclitaxel. 1,5

    In this open, non-randomized, prospective study, 28 patients with stage 3 or 4 epithelial ovarian cancer were treated with Docetaxel/ CBDCA regimen and as the results indicate, there is a high clinical CR rate of about 35% and an overall remission rate of 92% which is very impressive. Out of the 10 patients with clinical CR who underwent second-look laparotomy, 4 (40%) had no macroscopic or microscopic evidence of residual disease which indicates a significant correlation between clinical assessment of results versus pathologic/2nd-look findings.

    The toxicity profile, particularly the neurotoxicity rate, is quite favorable compared with Paclitaxel/Platinum regimens. Our study indicates that first-line combination regimens with Docetaxel/ Carboplatin are feasible and efficacious and a large comparative randomized trial versus Paclitaxel is needed to answer some important questions regarding the best Taxane for epithelial ovarian cancer. 1,5

    References

    1. Vasey PA. A feasibility study of a taxotere cis-platin combination of previously untreated advanced ovarian cancer. Pro Am Soc Clin Oncol 1997; 16: 1270.
    2. Verweij J, Clavel M, Chevalier B. Paclitaxel and Docetaxel not simply two of a kind. Ann Oncol 1994; 5: 495-505.
    3. McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and Cis-platin compared with Paclitaxel and Cis-platin in patients with stage 3 and stage 4 ovarian cancer. N Engl J Med 1996; 334: 1-6.
    4. Markman J, Hakes T, Barakat R, et al. Follow-up of MSK Cancer Center patients treated with Paclitaxel for refractory ovarian cancer. J Clin Oncol 1996: 14: 796-9.
    5. Kaye SB, Piccart M, Aapro M, et al. Phase 2 trials of Docetaxel in advanced ovarian cancer. An updated review. Eur J Cancer 1997; 33: 2167-70.

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