Feasibility and Toxicity of Weekly Paclitaxel-Carboplatin in 131 Patients with Pretreated and Non-Pretreated Solid Tumors

Abstract

Background: Chemotherapy with paclitaxel and carboplatin 3-weekly is active in many tumors. Major toxicities are myelosuppression and neurotoxicity. Weekly administration of taxanes allows high dose intensity with reduced toxicity. Patients and Methods: 131 patients with solid tumors were treated as outpatients with paclitaxel 75 mg/m² and carboplatin AUC 2–3 days 1, 8, 15 every 4 weeks irrespective of pretreatment and partly in neoadjuvant and multimodal concepts. Results: 125 patients (median age 58 years) were evaluable for response and toxicity, of whom 45 suffered esophageal carcinoma (19 patients in neoadjuvant treatment) and 31 non-small cell lung cancer. 49 patients were pretreated. 23 patients received concomitant radiotherapy of esophagus or lung in doses ranging from 40 to 60 Gy. We observed a low hematologic toxicity with 15.2% grade-III/IV leukopenia/granulocytopenia and 3.2% thrombocytopenia grade III/IV. Neurotoxicity grade II was reported in 14 patients. Main toxicity with radiotherapy was esophagitis grade II or III in 7 out of 23 patients. Overall response rate was 54.2%. 5 out of 19 patients treated neoadjuvantly for esophageal cancer reached a pathological complete response. Conclusions: Weekly paclitaxel and carboplatin is safe and feasible in outpatients and a high dose intensity can be achieved. The favorable toxicity profile allows treatment of elderly and pretreated patients. Response rate is high including pathological complete responses and responses appear quickly, making this therapy most suitable for multimodal and neoadjuvant treatments.

Weekly Paclitaxel and Carboplatin Combination Chemotherapy in Patients with Advanced Squamous Cell Carcinoma of the Head and Neck

“…Anemia occurred at a similar percentage, probably because of the slower kinetics of red blood cells and the multifactorial etiology of anemia in advanced SCCHN. Our toxicity results are in line with data from patients with different solid tumors [16] and SCCHN [17][18][19] receiving weekly paclitaxel-carboplatin, either alone or as part of an induction therapy and/or concomitant to radiotherapy.…”

“…Whereas in some docetaxel and cisplatin combination trials response and survival appear to exceed those of cisplatin and fluorouracil, adverse effects remain frequent, and better tolerated therapies are needed [14]. As suggested by studies on paclitaxel for lung cancer [15], weekly administration of carboplatin and paclitaxel was able to enhance dose intensity (DI), while still reducing the incidence of adverse events and the need for supportive therapy in patients with different solid tumors [16]. In patients with SCCHN, one recent publication and 2 abstracts report on weekly administration of carboplatin and paclitaxel, as induction therapy and/or concomitant to radiotherapy [17][18][19].…”

Management of Elderly Patients with Advanced Non-Small Cell Lung Cancer: A Single-Center Experience

“…Of note, the exact differentiation between worsening PS and toxicity as reasons for treatment termination was sometimes difficult in this retrospective analysis. Although these results do not allow to recommend a specific regimen to be used in elderly patients, our findings underpin the feasibility of attenuated doses of weekly carboplatin doublets, as previously reported by us and others [39,40,41]. Although higher doses of carboplatin and paclitaxel were more effective, they did not improve quality of life and were associated with increased toxicity compared to monotherapy in clinical trials [10].…”

Comparison of 1-Hour and 3-Hours Paclitaxel Infusion Pharmacokinetics: Results from a Randomized Trial

“…Myelotoxicity is a minor problem, slightly more intense in case of 3-h infusion. Because the 1-h infusion of PAC as weekly infusions with 80-100 mg/m 2 comes more and more into routine use [17,18], more information on the pharmacokinetics and -dynamics of this schedule should be available because up to now there is no approval from the federal authorities. The pharmacokinetics of total PAC were presented in detail in this publication, the pharmacokinetics of the unbound (free) PAC of these two schedules were published recently as well as the Chremophor EL pharmacokinetics [26].…”

“…The pharmacokinetics of a 1-h PAC infusion in the dose range 150-250 mg/m 2 showed only a moderate nonlinear disposition [16]. Meanwhile, a trend towards weekly paclitaxel administrations can be observed [17,18]. The reason for this may be that a relatively high dose intensity can be reached along with a rather low myelotoxicity.…”