Sequential, Alternating, and Maintenance/Consolidation Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Review of the Literature

Abstract

LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Describe the new chemotherapy design strategies (i.e., sequential, alternating, and maintenance/consolidation chemotherapy).2. Identify potential advantages and drawbacks of these new strategies in advanced NSCLC.3. Discuss the results of clinical trials testing sequential, alternating, and maintenance/consolidation chemotherapy in advanced NSCLC.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTA platinum-based doublet with a third-generation agent (paclitaxel, vinorelbine, gemcitabine, docetaxel) represents the standard first-line treatment for advanced nonsmall cell lung cancer patients with good performance status (PS). Traditional chemotherapy provides response rates of 20%-40% and a median survival of 8 -10 months.In an attempt to improve its outcome, alternative schedules have been proposed, namely sequential, alternating, and maintenance/consolidation therapy. Sequential chemotherapy with a platinum-based doublet followed by a single agent is feasible in patients with good PS; preliminary results from randomized phase III trials with combination chemotherapy as a comparator are promising, suggesting similar efficacy and a better toxicity profile for the sequential arm. The use of sequential single agents is an option for elderly and frail patients unsuitable for a platinum-based combination.Based on trials published so far, it is unlikely that an alternating chemotherapy strategy will be proven superior to standard chemotherapy in patients with good PS. However, sufficient evidence exists that it could be appropriate in the elderly or in unfit individuals.Consolidation/maintenance chemotherapy may provide additional benefit for patients achieving disease control after standard first-line chemotherapy. Better results are seen when maintenance consists of an agent that has proven active in the induction phase. Further evaluation of this strategy, as well as of consolidation/maintenance therapy with targeted agents, is warranted.In conclusion, these approaches may improve the out-

Approval Summary: Pemetrexed Maintenance Therapy of Advanced/Metastatic Nonsquamous, Non-Small Cell Lung Cancer (NSCLC)

“…This is continued until disease progression. The rationale for such treatment is the Goldie-Coleman hypothesis that early use of noncrossresistant chemotherapy results in greater tumor cell death [16,17].…”

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Versus Placebo as Maintenance Therapy for Advanced Non-small-cell Lung Cancer: A Meta-analysis of Randomized Controlled Trials

“…The dosage of such drugs is normally very low. The duration of maintenance therapy is normally from the end of first-line therapy until the forced discontinuance due to disease (NSCLC) progression or occurrence of intolerable toxic reactions (Grossi et al, 2007). Up to date, although there is still a lot of controversy regarding the use of maintenance therapy, the concept still earns plenty of attention due to its great potential in delaying NSCLC recurrence and extending patient's survival (Quan et al, 2010).…”

Future Scenarios for the Treatment of Advanced Non-Small Cell Lung Cancer: Focus on Taxane-Containing Regimens

“…The switch from one treatment to another does not require documented progression and is generally independent of the response to the first part of the treatment sequence. This approach allows the delivery of a higher number of noncrossresistant drugs, both to optimize doses and to limit toxicities [43].…”

“…Overall, RRs are encouraging, in the range of 21%-55%, with mild toxicities [43]. Based on the results of a phase II study of gemcitabine-vinorelbine followed by sequential docetaxel [44], Kubota and colleagues conducted a randomized phase III study comparing a sequential regimen of first-line vinorelbine-gemcitabine followed by docetaxel with standard treatment with carboplatin-paclitaxel [45].…”