The Combination of Paclitaxel and Carboplatin as First-Line Chemotherapy in Patients With Stage III and Stage IV Ovarian Cancer

Abstract

The combination of paclitaxel 135 mg/m2 (24-hour infusion) and cisplatin 75 mg/m2 is now considered the standard treatment in first-line chemotherapy for stage III suboptimally debulked and stage IV ovarian cancer. Interest is focused on the possibility of evaluating the combination of paclitaxel with carboplatin, because it was found to be less nefrotoxic and less neurotoxic than cisplatin. This study seeks to determine the maximum tolerated dose and to assess the antitumor activity of the combination of a 3-hour paclitaxel infusion followed by carboplatin. Thirty-three chemotherapy-naive patients with stage III-IV epithelial ovarian cancer entered this open, nonrandomized dose-finding study. The first dose level investigated was paclitaxel 125 mg/m2 and carboplatin 250 mg/m2: the dose level progression was performed by alternatively increasing paclitaxel 25 mg/m2 and carboplatin 50 mg/m2. Cycles were repeated every 28 days. At least three patients were treated at each dose level. Overall, 233 and 224 cycles, respectively, are evaluable for nonhematologic and hematologic toxicity. Dose-limiting toxicities (febrile neutropenia and severe fatigue) were observed in two of six patients at level VIII (paclitaxel 225 mg/m2 and carboplatin 400 mg/m2) and therefore the previous dose-level (paclitaxel 200 mg/m2 and carboplatin 400 mg/m2) was considered as the maximum tolerated dose. Neutropenia (grade 3-4 in 63% of cycles), neurotoxicity (grade 2 in 37.5% and grade 3 in 9% of patients), arthromyalgias (grade 2 in 53% of patients and grade 3 in 3% of patients), and grade 3 alopecia were the most common toxicities observed. The incidence of thrombocytopenia was low (grade 3 in 4% of cycles) and no renal toxicity was observed. An objective remission was documented in 74% of 31 evaluated patients, including eight complete remissions (26%) confirmed by second-look surgery. The combination of paclitaxel 200 mg/m2 3-hour infusion followed by carboplatin 400 mg/m2 (30-minute infusion) is a safe and active regimen as first-line chemotherapy for advanced ovarian cancer.

Effectiveness of Carboplatin and Paclitaxel as First- and Second-Line Treatment in 61 Patients with Metastatic Melanoma

“…Combined chemotherapy with carboplatin and paclitaxel (CP) is a well established treatment regimen in advanced non-small-cell lung cancer and in advanced ovarian cancer [4]–[8]. Carboplatin replaced cisplatin from previous combined regimens demonstrating equal efficacy and less toxicity [9].…”

Evaluation of the cytotoxic and antitumour effects of the essential oil from Mentha x villosa and its main compound, rotundifolone

“…On the other hand, the spleen is an organ with important roles regarding the red blood cells and the immune system. Hepatic dysfunction induced by irinotecan, renal toxicity induced by docetaxel and haematopoietic suppression induced by 5‐FU are such examples [27–29]. In addition, often, vomiting and diarrhoea are observed, leading to loss of body mass and malnutrition.…”

“…Hepatic dysfunction induced by irinotecan, renal toxicity induced by docetaxel and haematopoietic suppression induced by 5-FU are such examples. [27][28][29] In addition, often, vomiting and diarrhoea are observed, leading to loss of body mass and malnutrition. Herein, variation in body mass, hepatotoxic and nephrotoxic effects, as well as changes in haematological parameters, were investigated.…”

Pegfilgrastim for the prevention of febrile neutropenia in patients with epithelial ovarian carcinoma—a cost-effectiveness analysis

“…The incidence of chemotherapy-induced FN in patients with advanced EOC varies substantially in the published literature from as low as 1% to as high as 11% with docetaxel containing regimens (5)(6)(7)(9)(10)(11)(12)(13) . Outside of clinical trials, there is limited data on the incidence of FN in patients with advanced EOC, especially in the taxane era.…”

“…Clinical estimates for the development of FN were obtained from a review of the published literature (Table 1) (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) . We attempted to use data from published phase II and III trials to estimate our probabilities.…”