A 61 year-old woman is presented at thoracic tumor board. She has a T4 N3 M0 squamous cell carcinoma of the left upper lobe. Staging studies (PET scan, MRI brain) are negative. The medical oncologist is recommending induction chemotherapy prior to chemoradiation. What is your recommendation regarding induction chemotherapy?
Locally Advanced Non-Small Cell Lung Cancer
Induction chemotherapy is not routinely administered prior to definitive concurrent chemotherapy and radiation for non-small cell lung cancer (NSCLC). In general, superior outcomes have not been demonstrated with this approach over definitive concurrent chemoradiation alone. For example, CALGB 39801 (Vokes et al. JCO 2007) randomized 366 patients with unresectable stage III NSCLC to 2 cycles of induction chemotherapy followed by thoracic chemoradiotherapy to 66 Gy or definitive chemoradiotherapy alone. Chemotherapy consisted of carboplatin (AUC 2) and paclitaxel (50mg/m2). There was no improvement in survival with induction (2-year overall survival was 29% for induction vs. 31% for definitive, p=0.3) and toxicity was worse with 38% of patients experiencing grade 3 or greater neutropenia during induction. Acute toxicities during radiotherapy including esophagitis, dysphagia, and dyspnea were similar between groups.
The evolution of treatment in locally-advanced NSCLC has been fairly linear. CALGB 8433 (Dillman et al. NEJM 1990 & JNCI 1996) and others demonstrated the survival benefit of sequential chemotherapy followed by radiotherapy over radiotherapy alone. RTOG 9410 (Curran et al. JNCI 2011) then demonstrated the superiority of concurrent chemoradiation over sequential chemotherapy followed by radiation. This represents the current standard of care for most patients.
In those with less nodal involvement (IIIA) and who are potential surgical candidates, Intergroup 0139 (Albain et al. Lancet 2009) asked a different question - Is there a benefit to induction chemoradiation followed by surgery versus definitive concurrent chemoradation. Overall, there was no improvement in survival. However, subgroup analyses suggest that patients who only require a lobectomy following induction chemoradiation may benefit from resection.