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


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

In This Article

Patients and Methods

The VCRT protocol consists of 2 cycles of cisplatin and vinblastine (each cycle delivered over three days), at 3-week intervals, followed by 2 further 3-day cycles of cisplatin and vinblastine administered concurrently with 60 Gy of radiation therapy over 30 fractions during cycles 3 and 4 (chemotherapy platform outlined in Table 1). Vinblastine dose during concurrent radiation is reduced to avoid excessive toxicity, primarily as esophagitis. Radiation treatment employed 3-dimensional conformal radiation therapy planning and consisted of 2 Gy of radiation per day to a total dose of 60 Gy. Treatment was given using an elective nodal irradiation approach, and therefore typically included mediastinal nodes. The primary tumor and gross lymph nodes received 60 Gy. Adjacent lymph nodes at risk received 45–50 Gy. Renal, hepatic, and hematologic parameters were deemed acceptable by the treating oncologist before the initiation of chemotherapy. To undergo VCRT radiation therapy, pulmonary function testing (PFT) with an forced expiratory volume in 1 second (FEV1) ≥ to 1.0 L, or > 45% of predicted was required; patients had not had previous radiation.

This retrospective analysis was a single institution study and a sole individual (EW) conducted the chart review. The Ontario Patient Information System (OPIS) is an electronic physician chemotherapy order entry system, and tracks the use of chemotherapeutic agents and protocols and was used to identify all LRCP patients treated with VCRT between 1996 and 2006. Although this database contains the stage established by the treating physicians, a 'corrected' clinical stage was determined during this chart review, using the American Joint Committee of Cancer (AJCC) Cancer Staging Manual, 6th Edition guidelines.[6] Because patients with stage IIIB NSCLC with malignant effusions (now M1) were excluded, as were patients with multilobe ipsilateral nodules (now T4), the stage groupings largely coincide with the International Association for the Study of Lung Cancer (IASLC) Lung Cancer Staging Project and the AJCC Cancer Staging Manual, 7th Edition.[7] The final stage reflected a conservative approach to downstage when the clinical stage was in question.

The diagnostic tests that each patient underwent during the initial staging and within the first month of treatment initiation were documented. Body surface area (BSA), the total dose of all chemotherapy with curative intent, and the total dose and number of fractions of radiation therapy were all recorded. All patients with "day 1" unresectable IIIA/IIIB NSCLC and the VCRT protocol designation, regardless of whether they completed therapy, were included in the analysis.

Toxicities from the VCRT protocol were evaluated by reviewing and interpreting laboratory reports, progress notes, nursing notes and assessment records, and patient phone calls; and graded from 1 to 4 using the National Cancer Institutes Common Terminology Criteria for Adverse Events v3.0 (CTCAE). If there was no documentation in the patient's chart to support a particular toxicity, it was assumed to have not occurred. As such, a conservative approach was used for uniformity when grading esophagitis, mucositis, and nausea and vomiting. Toxicities of interest such as cardiac events, neuropathy, and pneumonitis were attributed to VCRT when the initial onset was within 1 year of treatment completion.

In the small subset of 26 patients who underwent completion surgery within 6 months following VCRT, the type of surgery performed, any preoperative downstaging, and pathologic complete remissions were documented. However, completion surgery was not a planned intervention in the VCRT protocol.

Median survival time and OS were determined with Kaplan-Meier survival curves. Log-rank tests were conducted to compare survival between dichotomous groups of patients with respect to corrected clinical stage, body surface area, PFT's, histology, presence or absence of grade 4 toxicity, tumor size, completion surgery, radiation therapy received, and total cisplatin dose. Univariate analysis consisted of the Cox proportional hazards regression model to control for the following factors: body surface area, PFTs, tumor size, corrected stage IIIA, histology, completion surgery, radiation therapy, cisplatin dose, vinblastine dose, and grade 4 toxicity. The Kaplan-Meier method was used to generate survival curves comparing the survival of patients who received differing amounts of radiation therapy. Multivariable analyses were performed using the results of the univariate analyses to develop a proposed model to predict outcome.[8]