Using treatment interruptions to palliate the toxicity from concurrent chemoradiation for limited small cell lung cancer decreases survival and disease control

Background and Purpose: We analyzed the impact on survival outcomes of trea tment interruptions due to toxicity arising during the concurrent phase of chemotherapy/radio therapy (ChT/RT) for our limited-stage small-cell cancer (LSCLC) population over the past 10 years. Materials and Methods: From 198 9 to 1999, 215 patients received treatment for LSCLC, consisting of six cyc les of alternating cyclophosphamide/doxorubicin or epirubicin/vincristine ( CAV; CEV) and etoposide/cisplatin (EP). Thoracic RT was started with EP at either the second or third cycle (85% of patients). RT dose was either 40 G y in 15 fractions over 3 weeks or 50 Gy in 25 fractions over 5 weeks, deliv ered to a target volume encompassing gross disease and suspected microscopi c disease with a 2 cm margin. Treatment breaks arising during concurrent Ch T + RT were used to manage severe symptomatic or hematologic toxicities. We used the interruptions in thoracic RT as the 'marker' for any concurrent b reak and measured 'break duration' by the total length of time (in days) RT was interrupted, since that also signaled that ChT could be re-initiated. Patient results were analyzed for the impact of interruptions/treatment pro longation on overall and disease-free survival. Results: For all patients, 2-year and 5-year overall and disease-specific survivals were 22.7 and 7.2, 27.6 and 9.3%, respectively; overall and disease-specific median survivals were 14.7 months each. A total of 56 patients (26%) had treatment breaks d ue to toxicity. Hematologic depression caused the majority of breaks (88%). The median duration of breaks was 5 days (range 1-18). Patients with and w ithout interruptions were compared for a range of prognostic factors and we re not found to have any significant differences. Comparing interrupted/uni nterrupted courses, median survivals were 13.8 versus 15.6 months, respecti vely, and 5-year overall survivals were 4.2 versus 8.3%. respectively. Ther e was a statistical difference between overall survival curves which favore d the uninterrupted group (P = 0.01). When comparing a series of prognostic variables, multivariable analysis found that the most significant factor i nfluencing survival in the present study was the presence of treatment brea ks (P = 0.006). There was a trend for development of any recurrence in the patients with breaks (P = 0.08). When controlling for the use of prophylact ic cranial irradiation (PCI) in the two groups, the rate of failure in the chest was higher in the patients with RT breaks (58 vs. 33%). The rate of f ailure in the brain was dependent on the use of PCI only. Conclusions: Inte rruptions in treatment to palliate the toxicity from concurrent chemo radia tion result in poorer local control and decreased survival. (C) 2001 Elsevi er Science Ireland Ltd. All rights reserved.