Untreated Extensive-disease Small-cell Lung Research Articles

Long-term outcomes in extensive disease small cell lung cancer patients treated without immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been approved as first-line treatment for patients with untreated extensive disease-small cell lung cancer (ED-SCLC). However, there are few reports about the long-term outcomes in patients with ED-SCLC treated without ICIs. Thus, we analyzed the long-term outcomes in patients with ED-SCLC. We retrospectively examined the medical records of patients with SCLC who were treated at our hospital between September 2002 and September 2019. The main inclusion criteria were as follows: (i) histological or cytological confirmation of SCLC, (ii) diagnosed with ED-SCLC and (iii) received chemotherapy, not including ICIs, as the first-line treatment. To assess the trends of treatment outcomes, we compared the survival outcomes between 2002-2010 (early) and 2011-2019 (late) groups. A total of 314 patients were included in this study. Patient characteristics at the time of first-line treatment were as follows: median age was 69years; 82% of the patients were male and 70% had a performance status of 0 or 1. The median follow-up time of overall survival (OS) was 7.4years, and 89% of the patients died. The median progression-free survival and survival time were 4.9 and 12.1months, respectively. Five-year survival rate was 2%. There was no significant difference in survival between the early and late groups. We found that the long-term outcomes in ED-SCLC patients treated without ICIs were poor. Prior to the approval of ICI treatment for ED-SCLC, there was no improvement in the OS for ~20years.

A Weekly Combination of Carboplatin and Irinotecan for Previously Untreated Extensive Disease Small-cell Lung Cancer, Results of a Minimum Follow-up of 3 Years: A Multi-center Phase II Trial JMTO LC02-02

We conducted a Phase II study to evaluate the efficacy and safety of a weekly combination of carboplatin and irinotecan regimen for patients with extensive disease small-cell lung cancer. Patients with previously untreated extensive disease small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0, 1 or 2, were enrolled in this trial. Carboplatin area under the curve of two and irinotecan (50 mg/m(2)) were administered on days 1 and 8 every 3 weeks. Treatment was continued up to a maximum of six cycles. The expected response rate was 85%, and this regimen was considered sufficiently positive if >45 responses were observed in the 55 patients. Between December 2003 and September 2006, 56 patients were enrolled and 55 patients were eligible. Of 55 patients, 6 complete remissions and 37 partial remissions were achieved, and the response rate was 78.2% (95% confidence interval: 64.6-87.9). Major Grade 3 or more toxicities were leukocytopenia 3, neutropenia 15, anemia 7, infection 5, diarrhea 3, anorexia 7, nausea 6 and pneumothorax 1. The median survival was 13.9 months (95% confidence interval: 11.8-18.5) and the median progression-free survival was 5.7 months (95% confidence interval: 4.9-7.4). This Phase II trial of a weekly combination of carboplatin and irinotecan for extensive disease small-cell lung cancer was not positive for a response rate that is considered to be worthy of further Phase III trial.

A phase 2 study of irinotecan, cisplatin, and simvastatin for untreated extensive‐disease small cell lung cancer

The objective of this study was to investigate the efficacy of simvastatin in combination with irinotecan and cisplatin in chemotherapy-naive patients with extensive-disease small-cell lung cancer (ED-SCLC). In this phase 2 study, 61 patients received treatment with irinotecan (65 mg/m(2) ) and cisplatin (30 mg/m(2) ) on Days 1 and 8 every 3 weeks until either death or disease progression occurred. Patients also received oral simvastatin (40 mg daily) during the course of chemotherapy. The primary endpoint was 1-year survival. Secondary endpoints included the response rate (RR), progression-free survival (PFS), and toxicity. The 1-year survival rate was 39.3%. The median overall survival (OS) was 11 months, and the median PFS was 6.1 months. Overall, the RR was 75%. The most common grade 3/4 toxicity was neutropenia (67%). Efficacy of the treatment was associated significantly with smoking status. Compared with never-smokers, ever-smokers had a better RR (40% vs 78%; P = .01), a longer PFS (2.5 months vs 6.4 months; P = .018), and had a trend toward an improved OS (9.0 months vs 11.2 months; P = .095). The effect of smoking on survival was apparent when ever-smokers were subdivided according to pack-years (PY) of smoking. Ever-smokers who had smoked >65 PY had a significantly longer OS compared with ever-smokers who had smoked ≤65 PY or never-smokers (20.6 months vs 10.6 months vs 9.0 months, respectively; log-rank P = 0.032). In multivariate analysis, PY >65 was predictive of longer survival (hazard ratio, 0.280; 95% confidence interval, 0.113-0.694). The current results indicated that simvastatin in combination with irinotecan and cisplatin did not improve the survival of patients with ED-SCLC. Although the subgroup analysis by smoking status was exploratory, the addition of simvastatin to irinotecan and cisplatin may improve the outcome of heavy smokers with ED-SCLC.

Belotecan and Cisplatin Combination Chemotherapy for Previously Untreated Extensive-Disease Small Cell Lung Cancer

2 /day) on day 1 of a 3-week cycle. Results: Of the 19 assessable patients, 16 had an objective tumor response, including two complete responses, for an overall response rate of 84.2%. Toxicity was evaluated in all 20 patients who received a total of 106 cycles (median cycles/patient, 5.5; range, 1 ∼9). The major grade 3/4 hematologic toxicities were neutropenia (67.9% of cycles), anemia (19.8% of cycles) and thrombocytopenia (33.9% of cycles). No grade 3/4 non-hematologic toxicities were observed. No treatment-related deaths occurred. The median progression-free and overall survivals were 7.06 months (95% confidence interval (CI), 3.98 ∼10.14 months) and 9.96 months (95% CI, 6.12∼13.80 months), respectively. Conclusion: Combination chemotherapy with belotecan plus cisplatin is an effective treatment for ED-SCLC with acceptable hematologic and non-hematologic toxicities. (J Lung Cancer 2010;9(1):15 �� 19)

A phase II trial of fractionated irinotecan plus carboplatin for previously untreated extensive-disease small cell lung cancer

Irinotecan plus cisplatin has been previously documented to be effective in the treatment of extensive-disease small cell lung cancer (ED-SCLC). This study was undertaken to investigate the efficacy and feasibility of combination chemotherapy of irinotecan and carboplatin in previously untreated ED-SCLC. From December 2002 to October 2005, 39 patients with previously untreated ED-SCLC were enrolled. Patients were treated with irinotecan (50mg/m(2) IV on days 1, 8, and 15) and carboplatin (target AUC=5 IV on day 1) every 4 weeks for up to six cycles. Thirty-four patients (87.2%) were male and the median age was 65 years. ECOG performance status was 0-1 in 20 (51.3%) patients and 2 in 19 (48.7%) patients. The median number of chemotherapy cycles was six (range: 1-6 cycles). Thirty-five patients were assessable for response evaluation. The overall response rate was 69.2% (1 CR, 26 PR) under the intent-to-treat analysis. After a median follow-up of 22.7 months, the median time to progression was 6.4 months (95% confidence interval [CI]: 5.7-7.1 months) and median overall survival was 11.0 months (95% CI: 9.9-12.0 months). The estimated 1-year survival rate was 42.5%. In terms of toxicities, Grade 3/4 neutropenia and thrombocytopenia occurred in eight (25.6%) and five (15.4%) patients, respectively. Grade 3/4 non-hematologic toxicities included diarrhea (10.3%), anorexia (7.7%), infection (10.3%), and neutropenic fever (12.8%). There was one treatment-related death due to superimposed infection on the broncho-pleural fistula. The combination chemotherapy of irinotecan and carboplatin was effective and tolerable in previously untreated ED-SCLC patients.

A randomised phase II study of the efficacy and safety of intravenous topotecan in combination with either cisplatin or etoposide in patients with untreated extensive disease small-cell lung cancer

Topotecan (Hycamtin is active in small-cell lung cancer (SCLC). This phase II study investigated the efficacy and safety of topotecan in combination with either cisplatin or etoposide in untreated extensive disease SCLC (ED SCLC). Patients with untreated ED SCLC were randomised to treatment with T/C (topotecan 1.25mg/(m(2)day) IV days 1-5, cisplatin 50mg/m(2) IV day 5; 41 patients) or T/E (topotecan 0.75 mg/(m(2)day) IV days 1-- 5, etoposide 60 mg/(m(2)day) IV days 1-5; 41 patients) every 21 days. Response was evaluated by strict radiological criteria. Response rates were similar for T/C (63.4%, 95% CI: 48.7-78.2%) and T/E (61.0%, 95% CI: 46-76%) with one patient in each arm who underwent complete response. Median survival was 41.6 weeks (9.6 months) for the T/C group and 43.7 weeks (10.1 months) for the T/E group. Toxicity was primarily haematological in both groups. The proportion of patients with grades 3-4 anaemia was significantly higher in the T/C arm (46.4%) versus 20% with the T/E arm (p=0.018). The proportion of patients with grade 4 neutropenia was not significantly lower with T/C (56.1%) than with T/E (65.0%, p=0.41), as was the incidence of associated events such as sepsis (T/C: 0%; T/E: 9.8%, p=0.11). The overall deliverability of either regimen was similar. The most frequent non-haematological adverse experiences of all grades per patient were nausea (T/C: 43.9%; T/E: 36.6%), and alopecia (T/C: 39.0%; T/E: 56.1%). Topotecan did not appear to increase the frequency of adverse events specifically associated with cisplatin. This study showed T/C and T/E to be effective and well tolerated in patients with ED SCLC and further evaluation of topotecan in first line SCLC is warranted.

Irinotecan and etoposide for previously untreated extensive-disease small cell lung cancer: A phase II trial of West Japan Thoracic Oncology Group

Irinotecan is a topoisomerase I inhibitor that is highly active against small cell lung cancer (SCLC). Etoposide is another drug that is effective for SCLC. Since combination of these two topoisomerase inhibitors revealed a synergistic effect in vitro and showed a safety in phase I study, we conducted a phase II study in patients with previously un-treated extensive disease (ED) SCLC to evaluate the efficacy and toxicity of this combination. Fifty patients with previously untreated ED-SCLC were enrolled. Irinotecan was administered intravenously at 60mg/m(2) on days 1, 8, and 15, while etoposide was given at 80mg/m(2) on days 2-4. Treatment was repeated every 4 weeks for four cycles. The overall response rate was 66.0%, with a complete response rate of 10.0%. The median survival time was 11.5 months and the 1- and 2-year survival rates were 43.2 and 14.4%, respectively. The major toxicity of this regimen was myelosuppression, including grade 3 or 4 neutropenia (62.9%), leukopenia (28.0%), and anemia (14%). The other grade 3 toxicity was diarrhea (2%). This irinotecan and etoposide regimen is active against ED-SCLC with relatively mild toxicity.