Front-line paclitaxel and irinotecan combination chemotherapy in advanced non-small-cell lung cancer: a phase I–II trial

Abstract

Our purpose was to determine the efficacy of irinotecan plus paclitaxel administered on day 1, repeated every 2 weeks, in untreated patients with advanced or metastatic non-small-cell lung cancer (NSCLC). In total, 56 patients with inoperable or metastatic stage III and IV NSCLC with a histologically or cytologically confirmed diagnosis were enrolled. None of the patients had undergone prior chemotherapy or radiation therapy. Treatment involved irinotecan 125 mg m À2 and paclitaxel 135 mg m À2 administered on day 1 and repeated every 2 weeks for a planned number of nine cycles. With a standard dose of paclitaxel at 135 mg m À2 , the dosage of irinotecan was escalated at four levels: 75, 100, 125 and 150 mg m À2 ; 125 mg m À2 was established as the maximum tolerated dose; this dosage was administered to 46 patients. A total of 52 patients (median age 65 years, range 38 -77 years) were assessable for toxicity and survival and 46 for response rate. Out of 46 evaluable patients, 19 achieved partial response (41.3%), 17 had stable disease (37%) and 10 (21.7%) experienced disease progression. The median duration of response was 6 months (range 2 -9 þ months). The main adverse reactions were myelotoxicity (grades 3 and 4) in 10 (19.2%) patients and diarrhoea (grade 3) in four (7.7%) patients. Irinotecan combined with paclitaxel, administered every 2 weeks, appears to be an effective treatment for advancedstage NSCLC.

Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: A phase I-II trial

“…These findings show that the combination of chemotherapy agents based on pemetrexed do produce a long median or overall survival in advanced or metastatic NSCLC. This survival time has been seen in other chemotherapy combinations [15,[37][38][39]. However, the majority of the studies concerning trials of chemotherapy combinations for NSCLC do not achieve a median survival longer than 10-11 months [8,12,14,[40][41][42][43].…”

“…During recent years, cytotoxic agents such paclitaxel [4,5], docetaxel [6,7], gemcitabine [8,9], vinorelbine [10,11], carboplatin, a cisplatin analogue [12,13], plus some other agents such as irinotecan [14,15] and tirapazamine [16] have been tested in combination chemotherapy trials over the last decade. These trials aimed to increase median and overall survival and to reduce the adverse reactions of previous chemotherapy combinations (mainly those including nephrotoxic cisplatin).…”

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).…”

Paclitaxel-induced apoptosis is blocked by camptothecin in human breast and pancreatic cancer cells

“…targeting two different cellular proteins simultaneously by a combination of two compounds should, in theory, lead to increased cell death. In fact, clinical trials have been conducted to assess the efficacy of PTX and topo I inhibitors as a combination therapy against cancer (8,15,16). However, pre-clinical in vitro efficacy studies on the PTX and topo I inhibitor combination have yielded conflicting results.…”

“…currently, ptX is used to treat multiple cancer types, including ovarian, breast, head and neck, and lung tumors (5). PTX has shown varied clinical efficacy in combination with several cancer therapeutics such as trastuzumab (Herceptin ® ), carboplatin, cisplatin, 5-fluorouracil, gemcitabine and topoisomerase I (topo I) inhibitors (1,(6)(7)(8).…”