3-weekly paclitaxel-carboplatin with radiation for stage III NSCLC – option during COVID-19 pandemic

ABSTRACT

Purpose or Objective: The optimal choice and schedule of chemotherapy (CT) given concurrently with radiation (RT) for primary treatment of stage III unresectable non-small cell lung cancer (NSCLC) remain debatable. 3-weekly paclitaxelcarboplatin (PC) is a convenient schedule but not well studied. This study aims to review the efficacy, toxicities and prognostic factors for treatment outcomes of this regime. Materials and Methods: Patients with unresectable stage III (AJCC TNM 7th edition) NSCLC treated with radical chemoradiotherapy using 3-weekly PC (P 175mg/m2, C AUC=5 on day 1 of 21-day cycle) from January 2007 to April 2017 were retrospectively reviewed. RT was given 5 days per week in 2 Gy daily fractions to the planning target volume using 3D-conformal technique. Total of 4 to 6 cycles of CT were allowed at clinicians’ discretion. Patients who had >2 CT cycles before RT, <1 cycle of CT concurrently with RT and total RT dose < 60 Gy were excluded. Results: A total of 65 patients with median age 63 years (range 45-74 years) were included. Stage distribution was similar between IIIA (53.8%) and IIIB (46.2%). Majority (41.5%) of patients had adenocarcinoma, followed by squamous histology (38.5%). Most patients received 60 Gy of RT (96.9%) and 4 cycles of CT (83.1%). At a median follow up of 29.5 months (mo) (Interquartile range 13.4-53.6 mo), the median overall survival (OS) was 35.0 mo (95% CI 17.5-52.4 mo) and the median progressive free survival (PFS) was 12.2 mo (95% CI 8.7-15.8 mo). The 1, 3 and 5-year OS rates were 76.9%, 48.3% and 29.7% respectively. Multivariate analyses showed that gross tumour volume (HR 1.005 [95% CI 1.002-1.008];p<0.01), mean heart dose ≥ 5 Gy (HR 2.507 [95% CI 1.293-5.108];p< 0.01) and more than 4 cycles of CT given (HR 3.830 [95% CI 1.479-9.921];p <0.01) were independent prognostic factors for worse OS, while ≥ grade 2 esophagitis was an independent prognostic factor for worse PFS (HR 2.563 [95% CI 1.031-6.370];p=0.04). The maximum grade toxicity was grade 2 in 20 patients (41.5%), grade 3 in 27 patients (20.0%) and grade 4 in 5 patients (7.7%). No grade 5 events were observed. The most common grade 3 or 4 toxicity was neutropenia, which occurred in 9 (13.8%) and 5 (7.7%) patients respectively. Neutropenic fever was seen in 3 patients (4.6%). Grade 2 or above pneumonitis and esophagitis occurred in 5 (7.7%) and 9 (13.8%) patients respectively. (Figure Presented) Conclusion: Radical chemoradiotherapy using 3-weekly PC for unresectable stage III NSCLC is well tolerated, with comparable outcomes to historical data and less hospital visits which is preferred during the COVID-19 pandemic. Prospective studies evaluating whether this regime in combination with more sophisticated RT techniques to lower the cardiac and esophageal doses could improve the survival outcomes and further enhance the therapeutic ratio in the era of consolidative durvalumab are warranted.