Analysis of a Novel Protocol of Combined Induction Chemotherapy and Concurrent Chemoradiation in Unresected Non–Small-cell Lung Cancer: A Ten-year Experience with Vinblastine, Cisplatin, and Radiation Therapy

Eugenie Waters; Brian Dingle; George Rodrigues; Mark Vincent; Robert Ash; Rashid Dar; Richard Inculet; Walter Kocha; Richard Malthaner; Michael Sanatani; Larry Stitt; Brian Yaremko; Jawaid Younus; Edward Yu

Disclosures

Clin Lung Cancer. 2010;11(4):243-250. 

In This Article

Abstract and Introduction

Abstract

Background: The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non–small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients.
Patients and Methods: We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients.
Results: A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3–4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation therapy, and cisplatin dose. Similarly, Univariate Cox regression showed that completion surgery, use of radiation therapy, cisplatin dose, and vinblastine dose were associated with increased survival.
Conclusion: This retrospective analysis of a large cohort of patients reveals an OS for VCRT comparable to that reported in the literature for other current combined chemoradiation protocols. The success of this protocol seems to be dose dependent and the outcomes in those who underwent completion surgery suggests that pathologic complete remission is possible for IIIA and IIIB NSCLC.

Introduction

Stage III non–small-cell lung cancer (NSCLC) is a heterogeneous group of patients with mediastinal lymph node involvement or direct spread to extra pulmonary structures, but without evidence of distant metastases.[1] Because the majority of patients with IIIA or IIIB NSCLC are often deemed to have unresectable disease, the primary treatment modalities consist of radiation therapy for local disease, and chemotherapy for systemic micrometastatic disease and to act as a radiosensitizing agent.[2] In patients who have unresectable disease without malignant effusions, and a radiation treatment volume which is not excessive (and therefore without multiple nodules in other lobes), but are otherwise medically fit, the standard of care for IIIA and IIIB NSCLC has evolved from radiation therapy alone, to sequential chemoradiation, to current guidelines recommending concurrent chemoradiation.[1] Cisplatin is a radio-sensitizer, and clinical practice guidelines advise concurrent chemoradiation using cisplatin-based chemotherapy and thoracic radiation with a minimum of 60 Gy in 30 fractions administered over 6 weeks.[3] Although acceptable cisplatin-based regimens include combinations with etoposide, vinorelbine, or vinblastine, strong evidence for the use of 1 combination in particular does not exist in the literature.[3] Similarly, the optimal schedule for combined chemoradiation and the value of both induction and consolidation chemotherapy remains to be determined.

This retrospective analysis was undertaken to examine the outcome of a unique schedule of induction plus concurrent chemoradiation that was initiated at the London Regional Cancer Program (LRCP) in 1996. In search of an alternative to the former sequential (non-concurrent) dosing of vinblastine and cisplatin followed by radiation therapy, a phase I dose escalation study was conducted to develop a new concurrent schedule for combined chemoradiation therapy with cisplatin, vinblastine, and radiation therapy (VCRT).[4] The VCRT protocol was developed based on the chemoradiation (CT-RT) arm of the CALGB 8433 clinical trial (MST of 13.8 months and 5-year survival of 17%).[5] Following a phase II study to determine the optimal dosing schedule, the VCRT regimen has become the standard treatment protocol for unresectable stage IIIA or IIIB NSCLC patients, without pleural effusion, and with an acceptable radiation treatment plan incorporating all known disease (not multilobe nodules) at the LRCP since 1996. VCRT is used to this day, at our center, in a subset of patients with IIIA and IIIB NSCLC receiving curative-intent chemoradiation. This retrospective analysis was conducted to understand how our patients fared compared with published results for similar patients treated with other reported treatment regimens and to characterize their toxicities and OS times with VCRT.

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