Docetaxel-carboplatin as first line chemotherapy for epithelial ovarian cancer

Abstract

Epithelial carcinoma of the ovary is one of the most common gynaecologic malignancies, and the fourth most frequent cause of cancer death in women (Yancik, 1993). The asymptomatic early stages of ovarian cancer mean that most patients have widespread disease at the time of diagnosis. Patients with FIGO stage III and IV disease and significant residual tumour masses after primary surgery can expect a 5-year survival rate of less than 10%, despite multiple courses of platinum-based chemotherapy (Omura et al, 1991).Until the mid-1990s, the combination of a platinum compound and an alkylating agent was considered best therapy for these patients, but a new standard of care emerged after the publication of trial GOG-111 in 1996 which was followed by the first reports of the INTERGROUP trial, OV10, in 1998(Piccart et al, 2000. Both these large, prospective randomized studies demonstrated that patients treated with cisplatin-paclitaxel in combination had significantly higher response rates, progression-free survival and overall survival compared with the previous standard treatment of cisplatin and cyclophosphamide. However, this higher efficacy was at the expense of greater toxicity. In GOG-111, 135 mg/m 2 paclitaxel was administered with 75 mg/m 2 cisplatin as an inconvenient 24-hour infusion, and neurotoxicity in particular was more frequently observed (28% vs 21%, P ≤ 0.05). Reducing the paclitaxel infusion time to 3 hours (with a concomitant increase in dose to 175 mg/m 2 ) in OV.10 produced a further increase in neurotoxicity, with 19.6% patients experiencing CTC grade III or IV sensory neurotoxicity, compared with 1% of patients receiving cisplatin-cyclophosphamide. Meta-analyses incorporating data on nearly 10 000 patients from 45 randomized trials suggested that the substitution of carboplatin for cisplatin was equally effective either as a single agent or in combination (Aabo et al, 1998). The addition of carboplatin to paclitaxel was expected to produce less emesis and neurotoxicity, but greater myelosuppression compared with cisplatin-paclitaxel. Seven phase I-II trials of carboplatin-paclitaxel combinations have been reported, involving 260 chemo-naïve ovarian cancer patients (Bookman et al, 1996;Lhomme et al, 1996;Bolis et al, 1997;duBois et al, 1997;Huizing et al, 1997;ten Bokkel Huinink et al, 1997;Siddiqui et al, 1997). Doses of carboplatin ranged from AUC 5-10, and paclitaxel from 120-250 mg/m 2 and almost all the trials used a 3-hour paclitaxel administration schedule. As expected the major toxicities in all studies were myelosuppression and neurotoxicity, however, an apparent reduction in the expected level of thrombocytopenia was observed in many of these trials, and an interaction at the megakaryocyte level rather than a pharmacokinetic interaction is thought to be responsible (Calvert et al, 1995). Antitumour activity was substantial, with response rates ranging from 70-100%.The direct comparison of carboplatin-paclitaxel with cisplatinpaclitaxel in a prospective, randomized trial as first-line t...

Focal Adhesion Kinase Silencing Augments Docetaxel-Mediated Apoptosis in Ovarian Cancer Cells

“…These findings suggest that FAK is a substrate for docetaxel via caspase-3, and its inhibition potentiates docetaxel's apoptotic effects on ovarian cancer cells. Docetaxel is being increasingly used in clinical settings due to its greater potency compared with paclitaxel (37,38) and lower risk of neuropathy (39,40). We and others have shown that for adjuvant therapy of ovarian carcinoma, docetaxel is at least as effective as paclitaxel in combination therapy with platinum but may have a better side effect profile (39,40).…”

Evaluation of Calvert's Formula for Dosage Adjustment of Carboplatin in Japanese Patients with Hormone Refractory Prostate Cancer

“…This formula is widely used in the treatment of several type of carcinoma. [23][24][25][26][27] Although it is generally considered that creatinine clearance does not accurately reflect the glomerular filtration rate, 11,12) creatinine clearance is frequently used instead because of the inconvenience of measuring the glomerular filtration rate directly. Actually, some reported an arrangement of Calvert's formula using creatinine clearance.…”

Ovarian Cancer

“…While these regimens have demonstrated impressive response rates in well-conducted phase II trials, none had been compared in a large randomized trial to the now-standard paclitaxel and carboplatin regimen. This year's ASCO presented two important studies, both containing over 1,000 patients, comparing the standard paclitaxel and carboplatin 329 Ovarian Cancer regimen to either docetaxel with carboplatin [2,3] or, alternatively, the triplet carboplatin, epirubicin, and paclitaxel [4]. The Scottish Randomized Trial in Ovarian Cancer (SCOTROC) investigators designed a trial that built on their previous phase II experience with docetaxel and carboplatin [2].…”

“…This year's ASCO presented two important studies, both containing over 1,000 patients, comparing the standard paclitaxel and carboplatin 329 Ovarian Cancer regimen to either docetaxel with carboplatin [2,3] or, alternatively, the triplet carboplatin, epirubicin, and paclitaxel [4]. The Scottish Randomized Trial in Ovarian Cancer (SCOTROC) investigators designed a trial that built on their previous phase II experience with docetaxel and carboplatin [2]. The current phase III trial compared 3-hour paclitaxel at 175 mg/m 2 with carboplatin to docetaxel at 75 mg/m 2 over 1 hour and carboplatin.…”