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Lower-Dose Chemo for SCLC: Comparable Results in Low PS Patients
Abstract & Commentary
Synopsis: In a phase II trial, the combination of low-dose carboplatin and paclitaxel was shown to be well tolerated by elderly and, or frail (ECOG performance status 2) patients with advanced small cell lung cancer. Response rates and survival were comparable to those published for other combinations.
Source: Neubauer M, et al. J Clin Oncol. 2004;22: 1872-1877.
Extensive small-cell lung cancer (esclc) accounts for approximately 20-25% of all lung cancer diagnoses.1 Between 50-75% of all patients with small-cell lung cancer (SCLC) have extensive disease. Despite significant improvements in diagnosis and therapy for the past 10 years, the prognosis for patients with ESCLC remains poor. Currently, the standard treatment for patients with ESCLC is combination chemotherapy with cisplatinum (or carboplatin) plus etoposide. However, previous studies have demonstrated high levels of toxicity with this treatment regimen, most notably in older patients or those who have a compromised performance status (PS). Since this is primarily a disease of older individuals, alternative combinations and dosing schemes need to be assessed. Neubauer and colleagues from the Kansas City Cancer Center examined 77 eligible patients with ESCLC (50.6% male, 9.4% white, 44.2% with a PS of 2, median age 74 years) between July 2000 and December 2001 with the goal of evaluating the effects of lower doses of carboplatin and paclitaxel (AUC = 2 and 80 mg/m2, respectively) within a shorter treatment time frame (administered on days 1, 8, and 15 of each 4 week cycle, continuing for up to 6 cycles). They were specifically interested in a group of patients that were considered relatively frail either due to advanced age or a compromised performance status. Participating patients were analyzed for 1-year survival, response rate (RR), time to progression (TTP) and safety of weekly paclitaxel plus carboplatin.
Sixty six of the 77 participants were assessable for response. Of these, 25 responded to treatment (one complete response and 24 partial responses), leading to a response rate of 38%. The estimated 1-year survival rate was 30% and the median survival was 7.2 months (range, < 1 to 24.4 months). The median TTP was 3.5 months (range, < 1 to 21.2 months) and the estimated progression-free survival rate was 8%. Neutropenia and fatigue were the most common grades 3 and 4 toxicities, occurring in 22.1% and 8.6% of participants, respectively.
Comment by William B. Ershler, MD
The current trial offers a new treatment regimen for older or frailer patients with extended disease small cell lung cancer. The regimen offers a relatively simple schedule, easily manageable in a community oncology office and the toxicities, although present, were considered less than more aggressive regimens (eg, cisplatin and etoposide). Yet, 36 of the evaluable patients had dose reductions on at least one occasion.
One concern regarding weekly paclitaxel in older patients is the common practice of using dexamethasone in relatively high doses (20 mg prior to each injection). The consequences of this have yet to be evaluated with regard to the immune and metabolic effects over the treatment course. With reduced dose paclitaxel and in elderly patients who are more likely to be immunocompromised, it is possible that lower doses of steroid would be required to prevent the hypersensitivity for which it is prescribed.
1. Ihde DC, et al. Cancer: Principles and Practice of Oncology (ed 5) 1997; 911-945.
William B. Ershler, MD INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert.