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IMPORTANCEAlthough the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for EGFR gene mutation-positive non-small cell lung cancer is well established, optimal dosing remains to be established, especially in elderly or frail patients.OBJECTIVE To investigate the efficacy and safety of low-dose erlotinib in elderly or frail patients with EGFR mutation-positive non-small cell lung cancer.DESIGN, SETTING, AND PARTICIPANTS Single-arm phase 2 trial with the Southwest Oncology Group (SWOG) 2-stage design that enrolled frail patients from 21 Japanese institutions after meeting the inclusion criteria. Chemotherapy-naive patients with EGFR-activating mutation-positive non-small cell lung cancer who were considered frail based on age, the Charlson Comorbidity Index, and Eastern Cooperative Oncology Group performance status were eligible for the study.INTERVENTIONS Patients were initially administered 50 mg/d erlotinib for 4 weeks, which was modified based on response or adverse events. Dose increase was permitted for patients with stable disease after 4 weeks. MAIN OUTCOMES AND MEASURESThe primary end point was the independent review committee-confirmed objective response rate (ORR) at the dose of 50 mg/d. The study also evaluated the pharmacokinetics of low-dose erlotinib and influence of ABCB1 gene polymorphisms.RESULTS Eighty patients were enrolled, with a median (range) age of 80 (49-90) years; 54 (68%) were men. An independent review committee confirmed a significant ORR of 60.0% (90% CI, 50.2%-69.2%). The disease control rate was 90.0% (90% CI, 82.7%-94.9%), median progression-free survival was 9.3 months (95% CI, 7.2-11.4 months), and median overall survival was 26.2 months (95% CI, 21.9-30.4 months). Mild adverse events were observed in some participants, with few patients exhibiting grade 3 or greater adverse events. Low-dose erlotinib treatment was temporarily suspended for 10 patients owing to adverse events. Five of 80 patients (6%) had their erlotinib dose reduced to 25 mg because of oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia. Two patients discontinued treatment because of adverse events (cutaneous ulcer and bone infection, and oral mucositis, respectively). There were no cases of interstitial lung disease or treatment-related deaths. The median (range) erlotinib plasma concentration was measured at 685 (153-1950) ng/mL. Seventy-three patients discontinued study treatment owing to disease progression (n = 60), death (n = 3), AEs (n = 4), and patient requests (n = 6). No clear association was observed between the pharmacokinetics of low-dose erlotinib and the treatment outcome.CONCLUSIONS AND RELEVANCE Low-dose erlotinib appears to be safe and effective in elderly or frail patients with EGFR mutation-positive non-small cell lung cancer and can be a valid treatment option.

The G8 questionnaire is a quick and easy-to-use screening tool. Several studies reported that the G8 questionnaire had a high sensitivity for predicting abnormalities in the full comprehensive geriatric assessment and predicted functional decline and survival in elderly cancer patients. The present study aimed to evaluate the role of the G8 questionnaire for predicting clinical outcomes and overall survival (OS) in elderly patients with lung cancer, who received chemotherapy or chemoradiotherapy. The data of 101 lung cancer patients aged ≥70 years, who were hospitalized between September 2011 and August 2014, were analyzed. Of these patients (median age, 77 years), 83 (82%) had impaired G8 scores. The proportion of patients with an impaired G8 score was significantly higher in patients aged ≥80 years than those aged <80 years (p = 0.04). All 18 patients with a normal G8 score possessed an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and none of the patients with a normal G8 score had an ECOG PS of ≥2 (p < 0.0001). An impaired G8 score tended to correlate with a relative dose intensity of <0.65 in patients who received chemotherapy or chemoradiotherapy (p = 0.05, odds ratio = 5.40). In the univariate analysis, an ECOG PS of ≥2 and an impaired G8 score were significantly associated with a poor OS (p = 0.009 and p = 0.003, respectively). Moreover, in the multivariate analysis, an ECOG PS of ≥2 (HR 2.55; 95% CI, 1.23–5.30; p = 0.01) and an impaired G8 score (HR 3.86; 95% CI, 1.44–13.36; p = 0.006) were remained independent prognostic factor for OS. G8 screening tool is useful for the prognostication of elderly lung cancer patients treated with chemotherapy. These finding suggest that the G8 questionnaire could be a useful tool in treatment decision-making to predict prognosis and prevent patients from receiving inappropriate anti-cancer treatment near the end of life.

BackgroundCompared with standard chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are more effective in patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, data comparing the efficacies of different EGFR−TKIs, especially regarding the presence of brain metastasis, are lacking.MethodsEGFR-TKI naive patients with recurrent or stage IIIB/IV NSCLC harboring EGFR mutations, excluding resistance mutations, were enrolled in this study. We retrospectively determined progression-free survival (PFS) using the Kaplan−Meier method with log-rank test in patients treated with either gefitinib or erlotinib, cumulative incidence of central nervous system (CNS) progression using the Fine and Gray competing risk regression model, and favorable prognostic factors for CNS progression by multivariate analysis.ResultsSeventy-seven EGFR-TKI-naive patients were started on either gefitinib (n = 55) or erlotinib (n = 22) in our hospital from April 2010 to April 2016. Among the patients with brain metastasis, PFS tended to be longer in the erlotinib than in the gefitinib group. In the analysis of cumulative incidence, the probability of CNS progression was lower in the erlotinib group than in the gefitinib group. Particularly, in a subgroup analysis of the patients with brain metastasis, there was a significant difference between the erlotinib and gefitinib groups (hazard ratio 0.25; 95% confidence interval, 0.08–0.81; p = 0.021). Of the prognostic factors for CNS progression evaluated, the absence of brain metastasis before EGFR-TKI therapy and receiving erlotinib (vs gefitinib) had a significantly favorable effect on patient prognosis.ConclusionAlthough this was a retrospective analysis involving a small sample size, erlotinib is potentially more promising than gefitinib for treatment of brain metastasis in patients with EGFR-mutant NSCLC.

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BackgroundThe role of irinotecan for elderly patients with LD-SCLC has been unclear, and the timing of TRT combined with chemotherapy has not been fully evaluated.MethodsPatients aged > 70 years with untreated, measurable, LD-SCLC, performance status (PS) 0–2, and adequate organ function were eligible. Treatment consisted of induction with carboplatin on day 1 and irinotecan on days 1 and 8, every 21 days for 4 cycles, and sequential TRT (54Gy in 27 fractions). Carboplatin doses were based on AUC of 4 and 5 (levels 1 and 2, respectively), with a fixed irinotecan dose (50 mg/m2). Primary objective of the phase II study was overall responce rate. ResultsForty-three patients were enrolled and forty-one were finally analyzed (median age: 75 years [range 70–86 years); males 31; PS 0/1/2, n = 22/18/1]. Two patients were excluded because of protocol violation (ascertained to be extensive disease). Twelve patients were accrued at phase I and the number of patients with carboplatin dose-limiting toxicities at levels-1 (n = 6) and −2 (n = 6) were 1(grade 3 hypertension) and 2 (grade 4 thrombocytopenia), respectively. The phase II trial was expanded to 29 additional patients receiving the level 1 carboplatin dose, total of 35 patients. The median number of chemotherapy cycles was 4 (range 1–4), and the median radiation dose was 54Gy (range 36–60). Toxicities were generally mild. There were 4 complete and 27 partial responses (response rate 88.6%). With a median follow-up of 52 months, the median progression-free and overall survival times of phase II were 11.2 and 27.1 months, respectively.ConclusionsInduction chemotherapy of carboplatin plus irinotecan and sequential TRT was well tolerated and effective for elderly patients with LD-SCLC. Additional confirmatory studies are warranted.Trial registrationTrial registration number: UMIN000007352 Name of registry: UMIN.Date of registration: 1/Dec/2006.Date of enrolment of the first participant to the trial: 6/Feb/2007.Clinical trial registration date: 1/Feb/2006 (prospective).Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3353-y) contains supplementary material, which is available to authorized users.

PurposeThis study aimed to establish the maximum tolerated dose of concurrent chemoradiotherapy (cCRT) with conventional administration of the docetaxel (D) plus cisplatin (P) (conv-DP) regimen.MethodsPatients (aged ≤70 years) with unresectable dry stage III non-small-cell lung cancer (NSCLC) and having performance status 0 or 1 and adequate organ function were eligible. They received radiotherapy (60 Gy in 30 fractions) once daily starting on day 2. Concurrent P (day 1; 60 mg/m2 at Levels 1–3, 80 mg/m2 at Level 4) and D (day 1; 30 mg/m2 at Level 1, 40 mg/m2 at Level 2, 50 mg/m2 at Levels 3–4) were administered every 4 weeks for 2–4 courses.ResultsEighteen patients were enrolled (stage IIIA/IIIB, 5/13 patients). Three cases of dose-limiting toxicity were observed in this study, although another 3 cases were added at Levels 2 and 3. Radiotherapy was completed in 15 patients. Seventeen patients received more than 2 courses of chemotherapy. Neither Grade 3/4 esophagitis nor severe hematological events were observed at Levels 1–4. However, dose escalation to Level 5 (P [80 mg/m2], D [60 mg/m2]) was stopped because the Level 5 dose was the recommended dose (RD) of chemotherapy alone for stage IIIB/IV NSCLC in Japan. Therefore, the RD was determined as D50/P80 mg/m2 in this cCRT. The objective response rate was 89 %, and the median survival time was 23.6 months.ConclusionscCRT with non-split DP was a tolerable and effective regimen, and RD was 50/80 mg/m2 every 4 weeks.

This regimen appears to be feasible and effective. Based on these results, a Phase II/III trial comparing carboplatin plus etoposide with carboplatin plus irinotecan for elderly patients with extensive disease small-cell lung cancer is being planned by the Japan Clinical Oncology Group.