The feasibility of weekly paclitaxel in improving performance status(PS) of advanced non-small cell lung cancer (NSCLC) patients with poor performance status: A single-arm phase two trial.
Authors: Pathak Neha , Garg Rakesh , Mohan Anant , kumar akash , Khurana Sachin , Pushpam Deepam , Pathy Sushmita , Yadav Mukesh , Prasad Chandra Prakash , Malik Prabhat Singh 
Published: June 2022

e21155

Background: Treatment of driver mutation negative metastatic NSCLC with poor PS (Eastern Cooperative Oncology Group[ECOG] PS of ≥2) is controversial. Preliminary data suggests poor PS patients also benefit from chemotherapy, with toxicity being a valid concern. We hypothesize PS of a patient may improve with chemotherapy if poor PS is due to high tumor burden rather than comorbidities. We designed a phase II single arm study to assess the feasibility of using abbreviated chemotherapy to improve the PS of stage IIIC/IV NSCLC patients of ECOG PS≥2. Methods: Adult patients with age≤65 years, Charlson’s comorbidity index < 9, serum albumin≥3.5g/dl, adequate bone marrow and organ function, & ECOG PS≥2 as judged by the worst score of three independent physicians were administered 3 doses of weekly paclitaxel at 60mg/m2/dose. ECOG PS was again assessed at 4th week. Primary end point was an improvement in ECOG PS by 1 point at 4th week assessment. Secondary endpoints were toxicity by Common Terminology Criteria for Adverse Events (CTCAE v 5.0), quality of life(QOL)assessment at baseline and 4 weeks by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and its lung cancer module, EORTC QLQ-LC13. Optimal Simon’s 2 stage design was used. In the first stage, 18 pts were to be accrued; if ≤ 2 responses were observed the study would be stopped. Else, 25 additional pts would be recruited to a total of 43 patients. The null hypothesis would have been rejected if ≥ 7 responses were observed. This design yielded a type I error rate of 0.05 and 80% power. Results: A total of 46 patients were included in the study, median age 56years(interquartile range 54-59), 34(74%) male, 12(26%) had comorbid conditions, 34(74%) had extrathoracic disease, squamous cell carcinoma was the most common histology(41%). ECOG PS distribution shown in table. Overall, 11 out of 46 patients(24%) showed improved PS, fulfilling primary end point. Further 7 patients had improved in PS beyond the time point of 4 weeks. Due to improved PS, 16 patients(35%) were able to receive standard platinum doublet. Any grade toxicity was seen in 85% of patients and 20% had grade 3/4 (most common: anemia and diarrhea). At a median follow up of 4.8m (95 % CI: 3.27-14.9), the median progression free survival was 3.3 months (95% CI: 2.36-5.6) and median overall survival 6.8months (95% CI 2.47-8.8). QOL improved significantly for global QOL, role functioning, pain, dyspnea, insomnia, pain in chest, pain in other parts & worsened for alopecia and sore mouth. Conclusions: Use of abbreviated chemotherapy is a useful, well tolerated strategy in carefully selected poor PS stage IIIC/IV NSCLC patients that leads to meaningful improvement in QOL. Clinical trial information: CTRI/2020/01/022617. [Table: see text]