The results with the addition of metronomic cyclophosphamide to palliative radiotherapy for the treatment of non-small cell lung carcinoma

Swaroop Revannasiddaiah, Subhash Chandra Joshi, Kailash Chandra Pandey, Madhup Rastogi, Mukesh Sharma, Manoj Gupta


Background: A considerable proportion of non-small cell lung carcinoma (NSCLC) patients are ineligible for radical therapies. Many are frail not to tolerate intravenous palliative chemotherapy either. These patients often receive palliative radiotherapy (RT), or supportive care alone. We intend to compare outcomes with palliative RT alone, versus palliative RT plus oral low dose metronomic cyclophosphamide.
Methods: Data was mined from 139 eligible NSCLC patient records. Comparisons were made between 65 patients treated from January 2011 to March 2013 with palliative RT (20-30 Gray in 5-10 fractions) alone, versus 74 patients treated from April 2013 to December 2014 with palliative RT plus oral metronomic cyclophosphamide (50 mg once daily from day of initiation of RT until at least the day of disease progression). Response was assessed after 1-month post-RT by computed tomography. Patients with complete or partial response were recorded as responders. For the determination of progression free survival (PFS), progression would be declared in case of increase in size of lesions, development of new lesions, or development of effusions. The proportions of responders were compared with the Fisher exact test, and the PFS curves were compared with the log-rank test.
Results: Differences in response rates were statistically insignificant. The PFS was significantly higher when metronomic chemotherapy was added to RT in comparison to treatment with RT alone (mean PFS 3.1 vs. 2.55 months; P=0.0501). Further histological sub-group analysis revealed that the enhanced outcomes with addition of metronomic cyclophosphamide to RT were limited to patients with adenocarcinoma histology (3.5 vs. 2.4 months; P=0.0053), while there was no benefit for those with squamous cell histology (2.6 vs. 2.6 months; P=1). At the dose of oral cyclophosphamide used, there was no recorded instance of any measurable hematological toxicity.
Conclusions: For pulmonary adenocarcinoma patients, the treatment with palliative RT plus oral metronomic cyclophosphamide is better than that with palliative RT alone. However, for pulmonary squamous cell carcinoma the addition of oral metronomic cyclophosphamide to palliative RT offered no benefit. Further studies with similar and different metronomic chemotherapy agents are justifiable.