A Phase II Study of Oxaliplatin, Pemetrexed, and Bevacizumab in Previously Treated Advanced Non-small Cell Lung Cancer

IntroductionSingle agent chemotherapy is standard for second and third line treatment of non-small cell lung cancer (NSCLC). Combination therapy to date has not proven to be superior to single agents in this setting, often adding toxicity without any additional efficacy. We investigated the activity and tolerability of the combination of oxaliplatin, pemetrexed, and bevacizumab in patients with previously treated advanced NSCLC.MethodsThis multicenter phase II trial evaluated the safety and efficacy of the combination of pemetrexed (500 mg/m2), oxaliplatin (120 mg/m2), and bevacizumab (15 mg/kg), given every 21 days, in patients with previously treated advanced NSCLC. Eligibility criteria included performance status 0 to 1, nonsquamous histology, and at least one prior chemotherapy regimen. Patients with treated brain metastases were allowed. The primary end point was response rate, with secondary endpoints of progression-free survival and overall survival.ResultsThirty-six patients were enrolled on this study. Treatment was well tolerated; the most common grade 3 toxicity was hypertension, which was easily managed with oral medications. The nine (25%) patients with treated brain metastases had no episodes of cerebral hemorrhage. Of the 34 patients evaluable for tumor response, none had complete response, nine (27%) had partial response, 15 (44%) had stable disease, and 10 (29%) had progressive disease. Median progression-free survival was 5.8 months (95% confidence interval 4.1–7.8 months) and median overall survival was 12.5 months (95% confidence interval 7.3–17 months).ConclusionsTreatment with oxaliplatin and pemetrexed in combination with the targeted antiangiogenic agent bevacizumab yielded promising efficacy with manageable toxicity in the previously treated advanced NSCLC population

Potential of 18F-FDG PET toward personalized radiotherapy or chemoradiotherapy in lung cancer

Purpose We investigated the metabolic response of lung cancer to radiotherapy or chemoradiotherapy by 18F-FDG PET and its utility in guiding timely supplementary therapy. Methods: Glucose metabolic rate (MRglc) was measured in primary lung cancers during the 3 weeks before, and 10–12 days (S2), 3 months (S3), 6 months (S4), and 12 months (S5) after radiotherapy or chemoradiotherapy. The association between the lowest residual MRglc representing the maximum metabolic response (MRglc-MMR) and tumor control probability (TCP) at 12 months was modeled using logistic regression. Results: We accrued 106 patients, of whom 61 completed the serial 18F-FDG PET scans. The median values of MRglc at S2, S3 and S4 determined using a simplified kinetic method (SKM) were, respectively, 0.05, 0.06 and 0.07 μmol/min/g for tumors with local control and 0.12, 0.16 and 0.19 μmol/min/g for tumors with local failure, and the maximum standard uptake values (SUVmax) were 1.16, 1.33 and 1.45 for tumors with local control and 2.74, 2.74 and 4.07 for tumors with local failure (p < 0.0001). MRglc-MMR was realized at S2 (MRglc-S2) and the values corresponding to TCP 95 %, 90 % and 50 % were 0.036, 0.050 and 0.134 μmol/min/g using the SKM and 0.70, 0.91 and 1.95 using SUVmax, respectively. Probability cut-off values were generated for a given level of MRglc-S2 based on its predicted TCP, sensitivity and specificity, and MRglc ≤0.071 μmol/min/g and SUVmax ≤1.45 were determined as the optimum cut-off values for predicted TCP 80 %, sensitivity 100 % and specificity 63 %. Conclusion: The cut-off values (MRglc ≤0.071 μmol/min/g using the SKM and SUVmax ≤1.45) need to be tested for their utility in identifying patients with a high risk of residual cancer after standard dose radiotherapy or chemoradiotherapy and in guiding a timely supplementary dose of radiation or other means of salvage therapy. Electronic supplementary material The online version of this article (doi:10.1007/s00259-013-2348-4) contains supplementary material, which is available to authorized users

Non-small Cell Lung Cancer in Octogenarians: Treatment Practices and Preferences

IntroductionAmong patients with non-small cell lung cancer (NSCLC), patients aged 80 or older have inferior survival. Treatment practices in this patient population are poorly described. In this report, we describe the treatment of a population of very elderly patients with NSCLC at a large teaching hospital.MethodsA retrospective chart review was performed of 111 outpatients with NSCLC aged 80 or older. Patient treatment regimens were evaluated for consistency with contemporaneous stage-specific guideline-recommended therapy (GRT). Attention was paid to how patient characteristics and attitudes influence therapy decisions.ResultsPatients characteristics included median age of 82.6 years (range, 80–92), 30% stage I–II, 39% stage IV, 59% performance status 0–1, 25% performance status ≥2 (performance status unavailable for 15%). Eighty-four percent of the patients received some form of antineoplastic therapy, and 11% were treated with best supportive care alone. Of 34 patients with localized disease, 53% underwent tumor resection and 38% received definitive radiation. Of 70 patients with stage III or IV disease, 36% received cytotoxic chemotherapy and 27% received oral targeted therapy alone. Thirty-two percent of patients received the stage-specific GRT. Of the patients who did not receive GRT, 26% electively refused the offered GRT and 74% were not offered GRT.ConclusionsThe vast majority of octogenarian patients with NSCLC receive antineoplastic therapy, but only one third of this population receives stage-specific GRT. Although many patients choose aggressive therapies, a small but clinically significant portion chose not to receive the offered GRT. More data are needed on appropriate therapy recommendations for this patient population