Phase II trial of paclitaxel, ifosfamide, and carboplatin in extensive- stage small cell lung cancer Mark A. Socinski *, Marcus A. Neubauer, Jairo Olivares, Steven Ketchel, Maureen Tynan, Martha Moore, Ji-Hyun Lee, Kim Davis, Michael Schell, David Garfield Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, and US Oncology, Houston, TX, USA Received 3 September 2002; received in revised form 25 November 2002; accepted 29 November 2002 Abstract Extensive-stage small cell lung cancer (ES-SCLC) remains a therapeutic challenge to the medical oncologists. We evaluated the triplet combination of paclitaxel (175 mg/m 2 over 1 h), ifosfamide (2.5 gm/m 2 over 1 h) and carboplatin (AUC /6over 0.5 h) (PIC) all given on day 1 of a 21 day schedule. Thirty-five patients were entered with a median age of 59 years (range 40  /79). The ECOG PS was 0  /1 in 86%. A median of 6 cycles were delivered (range 1  /6). The principal toxicity was neutropenia with 66% of patients experiencing grade 4 neutropenia. Only 9% of patients experienced febrile neutropenia. One treatment-related death (3%) due to neutropenic sepsis occurred. Non-hematologic toxicity was minimal. The overall response rate was 71% (15% complete response, 56% partial responses). Quality of life appeared to be stable across time. The median survival time was 9.5 months (95% confidence interval (CI), 6.7  /13.2 months) with a 1- and 2-year survival rates of 43% (95% CI, 26  /59%) and 16% (95% CI, 2 /30%). PIC has activity in ES-SCLC and is associated with a response rate and survival profile similar to other combinations in this disease setting. This regimen has a tolerable toxicity profile and a favorable and convenient administration schedule. # 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Small cell lung cancer; Paclitaxel; Ifosfamide; Carboplatin; Chemotherapy; Clinical trial 1. Introduction Small cell lung cancer (SCLC) accounts for approxi- mately 15% of the roughly 165 000 new cases of lung cancer seen annually in the US [1]. Extensive-stage (ES) SCLC comprises two-third of new cases and is generally considered sensitive to combination chemotherapy [1]. Despite high initial response rates, median survival times from recent phase III range from 9 /12 months with 2-year survival rates generally less than 10%. The regimen of etoposide in combination with a platinum (cisplatin or carboplatin) is generally considered the ‘standard of care’ although a recent phase III trial suggests improved survival with the combination of cisplatin/irinotecan [2]. Further evaluation of active agents in combination regimens attempting to overcome the intrinsic drug resistance seen in Extensive-stage small cell lung cancer (ES-SCLC) is warranted attempt- ing to improve survival and achieve palliation of disease-related symptoms. Recent phase III strategies investigated in the treat- ment of ES-SCLC have included either the addition of other active agents to the core doublet of a platinum and etoposide [3,4], substitution of etoposide with irinotecan in the core doublet [2], use of maintenance topotecan or etoposide following 4 cycles of the core doublet [5,6] and more dose-intense regimens [5,7,8]. Some of these strategies have yielded improved survival outcomes [2,7,8] while others have not [3  /6]. The combination of carboplatin/paclitaxel has been evaluated in SCLC patients refractory to cyclophosphamide, doxorubicin, and etoposide (CDE) [9]. In that trial, a 73.5% response * Corresponding author. Address: Multidisciplinary Thoracic Oncology Program, University of North Carolina, CB #7305, Chapel Hill, NC 27599-7305, USA. Tel.:  /1-919-966-4431; fax:  /1- 919-966-6735. E-mail address: socinski@med.unc.edu (M.A. Socinski). Lung Cancer 40 (2003) 91  /97 www.elsevier.com/locate/lungcan 0169-5002/03/$ - see front matter # 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0169-5002(02)00527-5