Phase1 study of cisplatin plus pemetrexed with erlotinib and bevacizumab for chemotherapy-naïve advanced non-squamous non-small cell lung cancer with EGFR mutations.

Background Cisplatin and pemetrexed are very effective against advanced non-squamous non-small cell lung cancer (NSCLC) without EGFR mutations. Erlotinib plus bevacizumab are highly effective against advanced NSCLCs with activating EGFR mutations. We performed this phase I 'Quartet Trial' to determine the safety and efficacy of all 4 agents as a first-line treatment for non-squamous NSCLC patients harboring activating EGFR mutations. Patients and Methods Patients received escalating quartet-agent doses every 3 weeks for 4 cycles. We examined the dose-limiting toxicity (DLT) to determine the maximum tolerated dose (MTD) and recommended dose (RD). Results Ten patients (3 men and 7 women) with a median age of 69 years were enrolled. Four and 6 patients had exon 19 and 21 mutations, respectively; 8 received maintenance therapy without unexpected or cumulative toxicities. One of 6 patients experienced grade 3 vagal reflex at 60 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab, which was designated the RD. Four patients experienced no DLT with 75 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab (designated the MTD); however, 3 underwent dose reduction due to severe toxicities (grade 3 gastrointestinal hemorrhage, skin rash, nausea, and febrile neutropenia) during induction chemotherapy. The most frequent DLT-phase adverse events were nausea, anorexia, and fatigue. The overall response rate was 100%. Furthermore, the progression-free and overall survival rates were 17.9 and 32.0 months, respectively. Conclusions This quartet chemotherapy regimen was tolerable and effective in our patient population (UMIN000012536).

Nanoparticle Albumin-bound Paclitaxel+Carboplatin Therapy for Small Cell Lung Cancer Combined with Squamous Cell Carcinoma and Interstitial Lung Disease.

It has recently been shown that nanoparticle albumin-bound paclitaxel (nab-PAC)+carboplatin (CBDCA) provides a favorable overall response rate in non-small cell lung cancer. This is the first case report of nab-PAC+CBDCA therapy in small cell lung cancer (SCLC). Our patient was a 72-year-old man with stage IV SCLC combined with squamous cell carcinoma and interstitial lung disease (ILD). We administered nab-PAC+CBDCA as a second-line chemotherapy. A partial response was evident after two cycles of chemotherapy, and no serious side effects occurred. The progression-free survival was 15 weeks. Second-line chemotherapy using nab-PAC+CBDCA was effective and well tolerated in an SCLC patient with ILD.

A Rare Case of Pleomorphic Carcinoma of the Lung Harboring an Anaplastic Lymphoma Kinase (ALK) Rearrangement.

Molecular testing for anomalies, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangement, is part of the current standard of care for non-small cell lung cancer, particularly adenocarcinoma. ALK rearrangement occurs most frequently in adenocarcinoma cells and rarely in non-adenocarcinoma cells. We herein report a rare case of pleomorphic lung carcinoma with ALK rearrangement in both its adenocarcinoma and spindle cell components. This case suggests the possibility of ALK rearrangement in pleomorphic carcinoma.

Relationship between progression-free survival and overall survival in patients with advanced non-small cell lung cancer treated with anticancer agents after first-line treatment failure.

AIM: The hazard ratio of progression-free survival (PFS-HR) generally does not reflect that of overall survival (OS-HR) in advanced non-small cell lung cancer (NSCLC) patients treated with first-line therapy. Short survival post-progression (SPP) better reflects the PFS-HR and OS-HR in simulations. We aimed to evaluate whether the PFS-HR reflects the OS-HR in NSCLC clinical trials for post-first-line treatments. METHOD: We reviewed clinical studies of post-first-line anticancer agents for NSCLC. We examined the sample size of the experimental arm (EA), median PFS (mPFS) or median time to progression in the EA, median overall survival (mOS) in the EA, the PFS-HR and the OS-HR. SPP was defined as the difference between mOS and mPFS. The association between mPFS and SPP, mPFS and mOS, and the PFS-HR and OS-HR was tested. We sought for the optimal point of correlation of PFS-HR and OS-HR by every 1 month of SPP. RESULTS: We identified 32 trials (34 arms). mPFS and mOS were weakly correlated (correlation coefficient [r] = 0.376; P = 0.0286). The PFS-HR and OS-HR were also moderately correlated (r = 0.415; P = 0.015). The maximum r value was 0.770 (SPP < 6 months; P < 0.0001) when we tested the associations between the PFS-HR and OS-HR for SPP using 1-month increments. The estimated regression equation at this point was OS-HR = 0.679 × (PFS-HR) + 0.349. CONCLUSION: The PFS-HR and OS-HR were strongly correlated in advanced NSCLC patients treated with post-first-line anticancer agents, with a SPP of less than 6 months.

[Denosumab for bone metastasis of thoracic tumors-preparation of a practice manual and evaluation of its effectiveness].

The anti-receptor activator of nuclear factor-kB ligand (RANKL) antibody denosumab is thought to be useful in the improvement of the quality of life of patients with bone metastasis from thoracic tumors, given the ease of its subcutaneous administration. However, attention has to paid to the onset of hypocalcemia when determining the optimal dosage, especially since data and methods on its prevention are limited. Our project team monitored serum calcium levels in patients receiving denosumab treatment, evaluated methods to supplement calcium and vitamin D in cases of hypocalcemia, and developed an evidence-based common manual. Subsequently, denosumab administration and hypocalcemia were evaluated as per the manual. Grade 3 hypocalcemia was observed in 2 cases before the preparation, with no new cases seen since adopting the new protocol in the manual. We conclude that the development of severe hypocalcemia associated with denosumab treatment can be avoided by prompt management of this condition in the early stages and by adopting measures listed in the practice manual.

Stratification of malignant pleural mesothelioma prognosis using recursive partitioning analysis.

PURPOSE: Prognostic factors and complicated prognostic models have been proposed for malignant pleural mesothelioma (MPM). This study was designed to stratify MPM prognosis by using a simple model. METHODS: Patients diagnosed with MPM in the past 10 years (n = 122) were examined retrospectively. Data on the presence of chest pain, performance status (PS), asbestos exposure, smoking status, white blood cell count (WBC), haemoglobin (Hb) concentration, platelet count (PLT), lactate dehydronate (LD), histology, stage, and date of death or censored status were collected. After the factors were examined in the univariate analysis, recursive partitioning analysis was performed. RESULTS: Statistically significant factors related to survival were the type of histology, stage, PS, WBC, PLT, Hb concentration, and LD. Histology, stage, PS, and Hb concentration were used in multivariate analysis. Stage and Hb concentration showed good statistical significance, whereas PS was borderline significant. The survival analyses were stratified into five groups by PS, stage, Hb concentration, and chest pain using recursive partitioning analysis. Group A comprised patients showing the most favourable prognoses (PS 0-2 and Hb concentration >12.1 g dL(-1) or PS 0-2 and Hb concentration ≤12.1 g dL(-1) without pain), and group B comprised the remaining patients. The median overall survival in groups A and B was 563 days (95 % confidence interval [CI] 502-779) and 157 days (95 % CI 115-224), respectively (hazard ratio of 5.44 [3.46-8.53, P < 0.0001]). CONCLUSIONS: The MPM patients with PS 0-2 and Hb concentration >12.1 or ≤12.1 g dL(-1) without chest pain had favourable prognoses.