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J. Sculier
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P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.07-005 - AVE plus Valproate for Refractory/Relapsing SCLC: A Phase II Study by the ELCWP (ID 142)
09:30 - 09:30 | Author(s): J. Sculier
- Abstract
Background:
Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) to platinum-etoposide remains disappointing. In vitro experiments are suggesting that valproic acid, by inhibiting histone deacetylases (HDAC), could increase apoptosis of SCLC cell lines exposed to doxorubicin, vindesine and bis(2-chloroethyl)amine. The primary objective of this phase II study is to determine if epigenetic modulation with valproic acid in addition to a doxorubicin, vindesine, cyclophosphamide (AVE) regimen may allow adequate improved 6-months progression-free survival (PFS) in refractory/relapsing SCLC.
Methods:
Patients (pts) with previously pathologically proven SCLC, either primary or secondary refractory to prior chemotherapy regimen including platinum derivatives and etoposide, Karnofsky performance status ≥ 60, adequate haematological, hepatic, renal, lung and cardiac functions were eligible. After central registration, pts received AVE (doxorubicin 45 mg/m², vindesine 3 mg/m², cyclophosphamide 1 g/m² every 3 weeks) plus daily oral valproic acid to obtain serum concentration in the range of the recommended values for the treatment of epilepsy (50-100 μg/ml). Response was assessed after 3 courses and responders continued treatment until best response, unacceptable toxicity or cumulative dose of doxorubicin > 500 mg/m². The trial was designed to show that 6-months PFS was > 18%, powering the trial to detect an increase to at least 39%. With this assumption, at least 43 pts assessable for PFS had to be registered (a 10%, b 10%).
Results:
From 11/2008 to 12/2013, 64 pts were registered of whom 6 were ineligible. The main characteristics of the 58 eligible pts were: male/female 38/20 pts, PS 60-70/80-100 17/41 pts, median age 60 years, 19 pts received two or more previous lines of CT. Seven pts did not receive any CT leaving 51 pts assessable for the primary endpoint. Objective response rate was 19.6% (95% CI 8.7%-30.5%). Median PFS was 2.75 months (95% CI, 2.46 to 3.61) and 6-months PFS was 6%. Median survival time was 5.9 months (95% CI, 4.7 to 7.5) with 6 and 12-months survival rates of 50% and 6%. As expected, toxicity was mainly haematological with 88% and 26% grade 3-4 neutropenia and thrombopenia, respectively.
Conclusion:
Despite an interesting response rate, the addition of valproic acid to AVE did not translate into adequate PFS in relapsing/refractory SCLC to platinum/etoposide. This regimen cannot be recommended for further investigation.
