PURPOSE: The effectiveness of gemcitabine-containing regimens in stage IV NSCLC stimulated a set of randomized phase II trials investigating gemcitabine plus either carboplatin, paclitaxel, or cisplatin as neoadjuvant (preoperative) treatment in patients with Stage I or II NSCLC. This report analyses the effect of these gemcitabine-based regimens on the pulmonary function tests, as well as the actual clinical impact in the neoadjuvant setting.
METHODS: The regimens included gemcitabine plus either carboplatin, paclitaxel, or cisplatin. PFT and dyspnea scores were obtained at baseline and post-chemotherapy and compared to one of several secondary endpoints, including ability to undergo surgical resection. Smoking history was classified as minimal (<10 pk-yr history), medium (10–30 pk-yr history), or heavy (>30 pk-yr history).
RESULTS: Only minimal changes were seen in FVC, FEV1, TLC, pH, pO2, and pCO2 after chemotherapy (not statistically significant). An 8% decline was seen in mean DLCO % (adjusted for Hg) from pre- to post-induction (P <.0001), but did not correlate with clinical symptoms. Baseline PFT scores varied with smoking status. Reduction in DLCO % associated with neoadjuvant chemotherapy was most pronounced in recent and heavy smokers. Only 2% (2/85, 95% CI= 0.4, 7.8) of patients eligible for surgery did not undergo surgery due to PFT reduction following chemotherapy. One patient in the study experienced a clinically significant respiratory toxicity (grade 3 dyspnea). Pulmonary toxicity was only statistically associated with male gender. However, 27% of patients met the protocol definition for pulmonary toxicity based on PFT results, and 14% had a predicted DLCO% of <40% (adjusted for Hg). Perioperative mortality after surgical resection was low (2.8%), and survival encouraging (70% 2 year survival).
CONCLUSION: The most commonly affected PFT parameter post chemo was the DLCO. While 15% of patients had a significant reduction in the DLCO post chemotherapy, it did not correlate with clinical symptoms nor did it impact on ability to undergo surgical resection. Lung impairment at baseline was correlated with smoking history.
CLINICAL IMPLICATIONS: In the preoperative setting, gemcitabine-based chemotherapy was well tolerated.
DISCLOSURE: M Rivera, Grant monies (from industry related sources) This study was sponsored by Eli Lilly and Company.; Employee Some employees of Eli Lilly and Company are authors of this abstract.; Consultant fee, speaker bureau, advisory committee, etc. Some authors of this abstract have received honoraria from Eli Lilly and Company.; No Product/Research Disclosure Information