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Efficacy of Rechallenge Chemotherapy in Patients With Sensitive Relapsed Small Cell Lung Cancer.

Am J Clin Oncol. 2013 Feb 5;

Authors: Wakuda K, Kenmotsu H, Naito T, Akamatsu H, Ono A, Shukuya T, Nakamura Y, Tsuya A, Murakami H, Takahashi T, Endo M, Nakajima T, Yamamoto N

Abstract
OBJECTIVES:: To evaluate the efficacy of rechallenge with current induction regimens for sensitive-relapse small cell lung cancer (SCLC) patients. METHODS:: We defined sensitive relapse as treatment-free interval (TFI≥90 d). Sensitive-relapse SCLC patients who received second-line chemotherapy were separated into those treated with rechallenge chemotherapy (rechallenge group) and those treated with other regimens (other group). The endpoints were overall survival (OS), progression-free survival, and toxicity. RESULTS:: Sixty-five patients (19 rechallenge group and 46 other group) were assessable for efficacy and safety evaluation. No significant differences in age, sex, ECOG performance status at relapse, disease extent at diagnosis, or response to first-line treatment were found between the 2 groups, but TFI was significantly longer in the rechallenge group. Twenty-one patients of the other group received amrubicin. There was no significant difference in OS between the 2 groups [median survival time (MST): rechallenge group, 14.4 mo; other group, 13.1 mo; P=0.51]. In the patients treated with amrubicin, MST was 12.6 months. Comparing the rechallenge group with the patients treated with amrubicin, there was also no significant difference in OS (P=0.38). Both the rechallenge and other group included 11 patients with ex-sensitive relapse (TFI≥180 d). There was no significant difference in OS between the 2 groups (MST 15.7 vs. 26.9 mo, P=0.46). CONCLUSIONS:: Rechallenge chemotherapy did not prove superior to other chemotherapies, suggesting that monotherapy, such as amrubicin, might be reasonable as second-line chemotherapy for sensitive-relapse SCLC patients.

PMID: 23388567 [PubMed - as supplied by publisher]

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Efficacy and Safety of Oral Topotecan and Bevacizumab Combination as Second-Line Treatment for Relapsed Small-Cell Lung Cancer: An Open-Label Multicenter Single-Arm Phase II Study.

Clin Lung Cancer. 2013 Feb 4;

Authors: Spigel DR, Waterhouse DM, Lane S, Legenne P, Bhatt K

Abstract
BACKGROUND: Topotecan is currently the only US Federal Drug Administration (FDA)-approved drug for second-line treatment of relapsed small-cell lung cancer (SCLC). We investigated the efficacy and safety of a novel topotecan-bevacizumab combination in treating relapsed SCLC. PATIENTS AND METHODS: Each 21-day treatment cycle consisted of bevacizumab (15 mg/kg) administration on day 1 and oral topotecan (2.3 mg/m(2)/d) administration on days 1 to 5. Treatment was continued for 8 cycles or until disease progression/toxicity. The primary objective was evaluation of 3-month progression-free survival (PFS). Overall response rate (ORR), duration of response, time to response (TTR), and overall survival (OS) were secondary objectives. RESULTS: The study enrolled 50 patients between July 2008 and May 2010. The 3-month PFS was 65% (95% confidence interval [CI], 49.3%-76.9%), which was promising compared with the historical control of 50% (P = .017) but did not meet the predefined criteria for clinically meaningful improvement. Median PFS was 6.24 months for the sensitive subgroup (progression time from end of previous chemotherapy > 90 days; n = 27) and 2.91 months for the resistant subgroup (progression time ≤ 90 days; n = 23). No patient achieved complete response (CR), and the ORR was 16%. Twenty (40%) patients had stable disease (SD) and 13 (26%) had progressive disease (PD). Median OS, TTR, and duration of response were 7.4, 1.3, and 4.7 months, respectively. The worst reported adverse events (AEs) were grade 1/2 in 11 (22%) patients and grade 3/4/5 in 39 (78%) patients. CONCLUSION: Improvement in the 3-month PFS after treatment with topotecan-bevacizumab was promising compared with the historical control and justifies additional studies with this regimen.

PMID: 23391616 [PubMed - as supplied by publisher]

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A Retrospective Study of the Novel Combination of Paclitaxel and S1 for Pretreated Advanced Non-Small Cell Lung Cancer.

Chemotherapy. 2013 Jan 31;58(6):454-460

Authors: Aono N, Ito Y, Nishino K, Uchida J, Kumagai T, Akazawa Y, Okuyama T, Yoshinami T, Imamura F

Abstract
Background: Recently, multiple-line chemotherapy has become popular for non-small cell lung cancer (NSCLC). The survival time of patients is influenced by patient characteristics and subsequent treatments. Methods: The usefulness of paclitaxel plus S1 (PTX+S1) was evaluated in 46 pretreated NSCLC patients. Time from the start of individual regimens till the start of the next one (TNR) was calculated for regimens administered to the study population including PTX+S1 and analyzed by the shared frailty Cox model. Results: The response rate and the median progression-free survival time of PTX+S1 were 32.6% and 253 days, respectively. Substantial difference in TNR was observed in epidermal growth factor receptor mutation status and in line and type of regimens, but not in stage, age, sex, performance status and histology, by univariate analysis. Multivariate analysis revealed that PTX+S1 was only one factor to prolong TNR. Conclusion: Because of long progression-free survival and long TNR, further evaluation of PTX+S1 is necessary.

PMID: 23392470 [PubMed - as supplied by publisher]

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Radiotherapy versus best supportive care in patients with brain metastases and adverse prognostic factors.

Clin Exp Metastasis. 2013 Feb 8;

Authors: Nieder C, Norum J, Dalhaug A, Aandahl G, Pawinski A

Abstract
Several previous studies have suggested that patients with brain metastases should be treated with individualized approaches taking into account prognostic factors that influence survival. Whether or not radiotherapy represents overtreatment in patients with adverse prognostic features is currently being addressed in the randomized QUARTZ trial (best supportive care (BSC) vs. whole brain radiotherapy (WBRT)). However, inclusion is limited to patients with primary non-small cell lung cancer. Therefore, we analyzed a broader patient population with different primary tumors managed with BSC or WBRT (intended total dose 20 or 30 Gy). Survival was examined by uni- and multivariate analyses including matched pairs. Median overall survival of all 113 patients was 2 months. No significant difference between BSC and 20 Gy WBRT was observed. A slight but significant improvement was observed in the 30 Gy WBRT group (median 2.2 vs. 1.7 months). The magnitude of difference is not clinically meaningful. Subgroup analyses revealed that improved survival after 30 Gy WBRT was limited to patients with primary small cell lung cancer. In conclusion, these results confirm and extent interim results from the QUARTZ trial, suggesting that BSC is a reasonable choice in patients with limited survival expectation. Further efforts are necessary to improve identification of patients who are likely to benefit from WBRT, e.g. by refining available survival prediction tools, and to confirm that management of those with small cell lung cancer should include a less restricted use of WBRT.

PMID: 23392634 [PubMed - as supplied by publisher]