A Dose Finding Study of Carboplatin and Gemcitabine in Advanced Non-Small Cell Lung Cancer

Abstract

The excellent activity of the cisplatin-gemcitabine combination and favorable toxicological profile of carboplatin are the basis of carboplatin-gemcitabine combination therapy for non-small cell lung cancer. We carried out a dose-finding study with the aim of establishing the maximum tolerated dose (MTD) of carboplatin on day 1 in combination with gemcitabine at the dose of 1000 mg/m2 on days 1 and 8 in a 21-day cycle. The starting dose level for carboplatin was the area under the concentration time curve (AUC) 4 mg/ml/min. 18 patients were treated and a dose limiting toxicity was observed in 2 cases at the level of AUC 6 mg/ml/min. AUC 5 mg/ml/min was considered as the MTD for carboplatin in our regimen. Notably, 7 objective responses were observed.

Preparation, characterization, and cytotoxic effects of liposomal nanoparticles containing cisplatin: an in vitro study

“…However, cisplatin use is associated with severe side‐effects, especially nephrotoxicity . Extensive researches have been performed to develop novel chemotherapeutic agents as cisplatin substitute without nephrotoxicity including carboplatin and gemcitabine . Although these agents have not produced nephrotoxicity, other toxicities such as myelotoxicity are their main complications …”

Two consecutive days of treatment with liposomal cisplatin in non-small cell lung cancer

“…Renal toxicity was avoided with the use of these agents, but other side effects, including myelotoxicity, were observed. However, none of these agents were more effective when compared with cisplatin (15)(16)(17)(18)(19)(20)(21).…”

Lipoplatin Formulation Review Article

“…After 1990, new agents that did not cause nephrotoxicity were produced as a substitute for cisplatin. Agents such as carboplatin [11] paclitaxel, docetaxel, gemcitabine, vinorelbine, and irinotecan [12–15] were used either in combination or as substitutes for cisplatin [16, 17]. These agents succeeded in producing no nephrotoxicity but did produce other toxicities such as myelotoxicity, in comparison to cisplatin.…”

“…The main example was carboplatin, an analogue of cisplatin, which showed no renal toxicity but produced higher myelotoxicity than cisplatin. Carboplatin has often been used as a substitute for CDDP [11, 12] in lung [15], head and neck, and ovarian cancers [11]. The effectiveness of carboplatin was more or less equal to that of CDDP but not better.…”