Concurrent Chemoradiation Therapy with Docetaxel/Cisplatin Followed by Docetaxel Consolidation Therapy in Inoperable Stage IIIA/B Non–Small-cell Lung Cancer: Results of a Phase I Study

Rudolf M. Huber; Astrid Borgmeier; Michael Flentje; Jochen Willner; Michael Schmidt; Christian Manegold; Peter Bramlage; Jürgen Debus

Disclosures

Clin Lung Cancer. 2010;11(1):45-50. 

In This Article

Abstract and Introduction

Abstract

Introduction: Docetaxel consolidation therapy (DCT) after concurrent cisplatin/docetaxel chemoradiation therapy (CRT) produces high tumor control in non–small-cell lung cancer (NSCLC); toxicity is, however, considerable. We aimed to determine the maximally tolerated dose (MTD) for DCT.
Patients and Methods: Patients with inoperable stage IIIB NSCLC received docetaxel 20 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 22, 29, and 36, with concurrent radiation therapy 5 days per week for a total dose of 66 Gy. Patients achieving stable disease, partial response, or complete response were given DCT on days 71, 92, and 113. DCT was started with 75 mg/m2 and titrated depending on tolerability. The MTD of docetaxel was defined as the dose preceding that at which 3 or more patients experienced dose-limiting toxicity (DLT).
Results: Of 23 patients enrolled (median age, 58.8 years ± 7.3 years), 19 received complete CRT (4 withdrew because of toxicity). Of the patients receiving complete CRT, 1 patient died and 1 became operable, leaving 17 patients eligible for DCT starting at 75 mg/m2. After the third patient with DLT, dose was reduced to 60 mg/m2. Median survival was 27.6 months ± 23.1 months. Median TTP was 12.4 months ± 10.7 months.
Conclusion: The MTD of DCT after concurrent cisplatin/docetaxel CRT was determined to be 60 mg/m2, but toxicity was considerable. The benefit-risk ratio of DCT has, however, been questioned by a placebo-controlled phase III trial. Further phase III trials need to consider further stratification factors (pretreatment forced expiratory volume [FEV]1, hemoglobin, performance, and stage) to define a role for DCT in patients with NSCLC.

Introduction

Lung cancer is one of the most frequent tumors in Western societies, with about 42,000 patients being diagnosed every year in Germany alone. The prognosis is dismal, with an estimated 5-year survival rate of only 15% (1996–2003[1]). Approximately 80% of these patients have non-small-cell lung cancer (NSCLC) at diagnosis, the majority of which are squamous cell carcinomas. About one third of patients already have International Union Against Cancer stage IV disease at diagnosis, with palliative treatment options only. Although a further one-third is usually operable (stage I and II), a further one-third is unresectable.

Standard treatment for locally advanced unresectable NSCLCs is combined simultaneous chemotherapy and thoracic radiation, based, among others, on the phase III trials of Schaake-Koning et al,[2] Dillman et al,[3] Sause et al,[4] and Furuse et al.[5] Studies of docetaxel 20 mg/m2 and cisplatin 25 mg/m2 combinations in particular have shown good activity and acceptable toxicity, with esophagitis or mucositis being dose limiting.[6] Further studies reported benefit of chemotherapeutic induction therapy with docetaxel.[7,8] With respect to consolidation therapy, Gandara et al (S9504) have demonstrated that docetaxel consolidation therapy (DCT) after cisplatin/etoposide concurrent chemoradiation therapy (CRT) had favorable activity and survival with manageable toxicity (Table 1).[9,10] Though the dose of DCT was escalated from 75 to 100 mg/m2 in the absence of protocol-defined toxicity, recent work has shown that lower doses of 75 or even 60 mg/m2 might be equally effective but less toxic.[11–13] Taken together, however, the maximum tolerated dose (MTD) of DCT after cisplatin/docetaxel CRT is not well defined.

The primary objective of this study was to evaluate the MTD of DCT after cisplatin/docetaxel CRT. Secondary objectives were to assess overall survival (OS), time to progression (TTP), response rate, and toxicity.

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