Induction chemo increases survival in unresectable NSCLC

HOUSTON—Pretreatment with induction chemotherapy appears to give certain inoperable non-small-cell lung cancer (NSCLC) patients who undergo radiation and concurrent chemotherapy (chemoradiation) a small but statistically significant increase in overall, 5-year, and distant-metastasis-free survival, compared with concurrent chemoradiation alone, the standard of care.

The findings emerged from a retrospective analysis of NSCLC patients treated at The University of Texas M.D. Anderson Cancer Center.

"The results of this study suggest that adding two or three cycles of induction chemotherapy may improve overall survival by reducing distant metastases without compromising local control," the authors reported in the July 1 issue of the International Journal of Radiation Oncology•Biology•Physics (68:779-785, 2007). "Our results for patients treated with concurrent chemoradiation alone were similar to those from the two randomized trials that established this approach as the standard of care."

265 Consecutive Patients

In their study, radiation oncologist Eugene H. Huang, MD, and his colleagues included 265 consecutive NSCLC patients treated with three-dimensional conformal radiation and concurrent chemotherapy, including 127 patients (48%) who received two or three cycles of induction chemotherapy using a dual-agent regimen prior to chemoradiation.

The induction group included 121 patients who received a platinum and taxane; the remaining 6 pretreated patients received cisplatin/etoposide, cisplatin/gemcitabine (Gemzar), or gemcitabine/vinorelbine (Navelbine).

The two groups did not differ with respect to age, weight loss, performance status, histology, grade, combined stage, T stage, N stage, or mediastinoscopic staging, Dr. Huang said.

The radiotherapy typically targeted the gross tumor volume and the involved lymph node stations in both patient groups with daily 1.8- or 2-Gy fractions (183 patients) or twice daily 1.2-Gy fractions (82 patients). Uninvolved lymph nodes were not irradiated.

Nine of the patients did not complete radiation treatment because of toxicity or disease progression and received less than 60 Gy. The median dose delivered was 63 Gy (range, 34.8 Gy to 72 Gy).

Concurrent chemotherapy consisted of a weekly platinum and taxane regimen (n = 165), weekly platinum and etoposide (n = 18), or cisplatin and etoposide for two cycles (n = 63). An additional 19 patients received a single-agent regimen consisting of a platinum, a taxane, or gemcitabine weekly. The median patient follow-up was 19 months (range, 3 to 80 months).

The study results significantly favored the induction chemotherapy arm in several key areas:

• Patients receiving induction chemotherapy had a median overall survival of 1.9 years vs 1.4 years for standard care, and a 5-year survival rate of 25% vs 12% (P < .001). A multivariate analysis showed that induction chemotherapy was the most significant factor affecting overall survival (HR 0.55, P < .001).

• The 5-year rate for distant-metastasis-free survival was 42% for the induction group vs 23% for the noninduction patients (P = .021).

• In patients with adenocarcinoma or large-cell carcinoma, induction chemotherapy was associated with a 5-year overall survival rate of 24% vs 8% for the standard therapy arm (P = .003). But there was no significant difference between the two groups in 5-year survival in patients with squamous cell carcinoma.

A multivariate analysis of patients with adenocarcinoma or large-cell carcinoma confirmed that induction chemotherapy was the most significant factor associated with better overall survival (HR 0.47, P = .003).

The authors concluded on the basis of their retrospective analysis that "induction chemotherapy followed by concurrent chemoradiation should be considered in the treatment strategies for patients with adenocarcinoma or large-cell carcinoma of the lung."