Phase II study of IRInotecan treatment after COmbined chemo-immunotherapy for extensive-stage small cell lung cancer: Protocol of IRICO study.

INTRODUCTION: Combined treatment using anti-programmed death-ligand 1 antibody (anti-PD-L1) and platinum-etoposide is the current standard first-line treatment for patients with extensive-stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES-SCLC after the first-line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES-SCLC, and treatment with irinotecan is well established as both a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second- or later-line setting for patients with ES-SCLC who have been previously treated with combined treatment. METHODS: Our study will enroll total 30 patients who are diagnosed with ES-SCLC and have experienced disease progression after the combined treatment. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m2 ) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator's decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression-free survival, and safety. DISCUSSION: Since the present first-line treatment has been changed to the combined treatment, the second- or later-line treatment should be re-evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This study demonstrates and re-evaluates the clinical benefits of irinotecan after combined treatment with anti-PD-L1 and platinum-etoposide for patients with ES-SCLC. REGISTRATION DETAILS: This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021.

Efficacy of S-1 after pemetrexed in patients with non-small cell lung cancer: A retrospective multi-institutional analysis.

BACKGROUND: S-1 and pemetrexed (PEM) are key treatments for non-small cell lung cancer (NSCLC). However, the mechanism of anticancer activity of S-1 and PEM is similar. Cross-resistance between S-1 and PEM is of concern. This exploratory study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment. METHODS: This retrospective study included patients with advanced (c-stage III or IV, UICC seventh edition) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at six hospitals in Japan. The primary endpoint of the study was the overall response rate (ORR). The secondary endpoint was the disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 53 NSCLC patients met the criteria for inclusion in the study. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidence interval [CI]: 0.00%-10.1%). Median TTF, PFS, and OS were 65, 84, and 385 days, respectively. CONCLUSIONS: Although there were several limitations in this study, the ORR of S-1 after PEM in patients with nonsquamous (non-SQ) NSCLC was low compared to the historical control. One of the options in the future might be to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.

Phase II study of nedaplatin and amrubicin as first-line treatment for advanced squamous cell lung cancer.

BACKGROUND: The first-line treatment for squamous cell lung cancer (SCC) has not necessarily been established; however, our previous exploratory study suggested that the combination of nedaplatin and amrubicin would be a promising treatment approach for patients with SCC. Therefore, a phase II study of this chemotherapeutic combination was designed to evaluate its efficacy and safety for treatment-naïve patients with advanced SCC. METHODS: A total of 21 treatment-naïve patients with stage IIIB/IV or postoperative recurrent SCC were enrolled from six institutions. Nedaplatin (100 mg/m2 ) on day 1 and amrubicin (25 mg/m2 ) on days 1-3 were administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR), while the secondary endpoints included overall survival (OS), progression-free survival (PFS), and drug toxicities. RESULTS: Partial response was observed in seven of 21 cases (ORR, 33.3%; 95% confidence interval [CI], 14.5-52.2). Disease control rate, which includes stable disease, was 71.4%. Median OS and PFS was 14.6 and 4.1 months, respectively. This regimen did not cause any treatment-related deaths. Grade 3/4 neutropenia developed in 8 of 21 cases (38.1%); however, febrile neutropenia developed in only 9.5% of the cases. Grade 3/4 gastrointestinal or neuromuscular toxicities were not observed. CONCLUSION: The efficacy of the combination of nedaplatin and amrubicin was comparable to that of other conventional chemotherapeutic regimens for treatment-naïve patients with advanced SCC, and no severe gastrointestinal or neuromuscular toxicities were observed. This combination therapy may be an alternative treatment approach, particularly in patients who cannot tolerate gastrointestinal or neuromuscular toxicities.

Fluctuation of Hepatic Focal Nodular Hyperplasia Size with Oral Contraceptives Use.

BACKGROUND Focal nodular hyperplasia (FNH) of the liver is a rare benign nodular lesion that arises in women of reproductive age. Although a role of female hormones has been suggested, their influence on the course of FNH has remained controversial. CASE REPORT A 44-year-old woman with a 12-year history of oral contraceptive use was referred to our hospital for examination of an asymptomatic liver mass (3 cm in diameter) identified by computed tomography. We diagnosed FNH using imaging methods and fine-needle biopsy. Oral contraceptives were discontinued because the mass increased over a period of 21 months. Four months later, the mass had decreased in size, indicating that FNH can spontaneously regress when oral contraceptives are discontinued. CONCLUSIONS Discontinuation of oral contraceptives use can reduce the size of FNH, as in this case.

Pharmacokinetic parameters of gefitinib predict efficacy and toxicity in patients with advanced non-small cell lung cancer harboring EGFR mutations.

PURPOSE: The relationship between plasma concentration and antitumor activity of gefitinib was assessed in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. PATIENTS AND METHODS: Plasma trough levels of gefitinib were measured on days 2 (D2) and 8 (D8) by high-performance liquid chromatography in 31 patients. Plasma concentrations of gefitinib were also measured 10 h after the first administration in 21 of these patients to calculate the elimination half-life of gefitinib. RESULTS: The median trough levels were: 197 ng/ml 10 h from the first administration of gefitinib; 113 ng/ml on D2; and 358 ng/ml on D8. The median D8/D2 ratio was 2.709, and the median elimination half-life was 15.7 h. The median progression-free survival (PFS) was 273 days, and the median overall survival (OS) was 933 days. A high D8/D2 ratio was significantly correlated with better PFS, though the plasma trough levels on D2 and D8 were not significantly related to PFS. The elimination half-life was not a significant factor for PFS, but it was significantly correlated with high-grade adverse events. Pharmacokinetic parameters were not significantly correlated with OS. CONCLUSIONS: A high D8/D2 ratio, but not elimination half-life, might be a predictor of better PFS in patients with NSCLC harboring EGFR mutations treated with gefitinib. On the other hand, long elimination half-life was related to high-grade adverse events in these patients. Clinical Trial Registration UMIN000001066.