A dose-escalation study of irinotecan (CPT-11) in combination with cisplatin in patients with advanced non-small cell lung cancer previously treated with a docetaxel-based front line chemotherapy

Purpose: A phase I study was conducted to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of a CPT-11 plus cisplatin combination as salvage treatment in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Twenty-two patients with histologically confirmed NSCLC, who had failed taxotere-based front-line chemotherapy, were enrolled. The patients’ median age was 61 years, 19 (86%) were male, and 17 (77%) had a performance status (World Health Organization (WHO)) 0–1. CPT-11 was administered as a 60-min i.v. infusion at a fixed dose of 100 mg/m² on day 1 and at escalating doses on day 8, starting from 100 mg/m² with increments of 10 mg/m² ; cisplatin was administered at a fixed dose of 80 mg/m² on day 8, 2 h after CPT-11 administration. Treatment was repeated every 3 weeks. Results: At the dose of CPT-11 120 mg/m² , three out of four enrolled patients presented DLTs (grade 4 neutropenia, febrile neutropenia and delayed diarrhea); the addition of G-CSF at this level did not permit further dose-escalation. Grade 3/4 neutropenia was observed in 12 (18%) cycles, febrile neutropenia in four (6%), and grade 3/4 thrombocytopenia in four (6%). Grade 3/4 diarrhea was seen in six (29%) patients, and grade 2/3 nausea and vomiting in 12 (57%). Neurotoxicity grade 2 was observed in six (29%) patients and grade 3 in one (5%). Other toxicities were mild. The MTD was CPT-11 100 mg/m² on day 1 and 110 mg/m² on day 8 in combination with CDDP 80 mg/m² on day 8. Among 12 patients evaluable for response, partial response was achieved in two (16.7%) patients and stable disease in five (41.7%). Conclusion: The combination of CPT-11 and cisplatin has substantial but manageable toxicity and marginal activity as salvage treatment of patients with NSCLC who have failed taxotere-based front-line chemotherapy; further investigation is warranted to define its precise role in the second-line setting.     

A pilot study of irinotecan hydrochloride(CPT-11)and cisplatin(CDDP)combination chemotherapy for previously treated non-small cell lung cancer

A pilot study of irinotecan hydrochloride(CPT-11)and cisplatin(CDDP)combination chemotherapy had been performed for previously treated non-small cell lung cancer. CPT-11(60 mg/m(2))and CDDP(30 mg/m(2))were administered on days 1 and 15 every 28 days, and the combination chemotherapy was repeated up to 4 courses. The efficacy and safety of this pilot study based on outpatient therapy were evaluated. Eleven patients were entered, and the median number of courses was 3 courses. Severe adverse reactions(grade 3 or higher)were 33% for neutropenia, and 9.1% for leukopenia, anemia, diarrhea, fatigue, and vomiting. A case with grade 3 diarrhea needed hospital admission for a short period, and thereafter outpatient therapy could continue. The efficacy of this study was 73% of SD and 27% of PD, and MST was 358 days. These results suggest that this protocol could be carried out as outpatient therapy, and may contribute to prolonged survival time.     

Salvage treatment of advanced non-small-cell lung cancer previously treated with docetaxel-based front-line chemotherapy with irinotecan (CPT-11) in combination with cisplatin

Background:A phase II study was conducted in order to determinethe toxicity and efficacy of the combination of CPT-11 and cisplatin, assalvage treatment in patients with advanced non-small-cell lung cancer(NSCLC), progressing after a docetaxel-based front-line regimen. Patients and methods:Thirty-one patients (median age 61 years)with NSCLC, were enrolled. Twenty-six (84%) patients were male,twenty-five (81%) had disease stage IV, and twenty-eight (90%)had a performance status (WHO) 0–1. CPT-11 was administered as a60-minute i.v. infusion at the dose of 100 mg/m² on day 1 and 110mg/m² on day 8; cisplatin was administered at the dose of 80mg/m² on day 8, after CPT-11 administration. Treatment was repeatedevery three weeks. Results:A total of 110 chemotherapy cycles were administered. Inan intention-to-treat analysis 7 patients (23%; 95% confidenceinterval (95% CI): 8%–37%) achieved a partialresponse, 6 (19%) had stable disease, and 18 (58%) progressivedisease. Three of responders had failed a previous docetaxel–carboplatincombination. The median duration of response was 3 months, the median TTP 8months and the median survival for the entire group 8 months. Grade 3–4neutropenia was observed in 16 (52%) patients and in two cases this wasfebrile. Grade 3 and 4 thrombocytopenia occurred in two (7%) patients,respectively. Grade 3 and 4 diarrhea was seen in 10 (33%) patients,grade 2–3 neurotoxicity in 2 (6%), and fatigue grade 2–3in 12 (39%). Other toxicities were mild. Conclusions:The combination of CPT-11 and cisplatin hasmanageable toxicity and interesting activity as salvage treatment of patientswith advanced NSCLC, previously treated with a docetaxel-based front-lineregimen.     

Phase II study of combination chemotherapy with gemcitabine and irinotecan in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens

OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of gemcitabine combined with irinotecan in patients with previously treated non-small-cell lung cancer (NSCLC). METHODS: Patients who failed to respond to platinum-containing first-line chemotherapy were enrolled and treated with gemcitabine 1000 mg/m(2) and irinotecan 150 mg/m(2) on days 1 and 15. Cycles were repeated every 4 weeks. RESULTS: Twenty-seven of 30 registered patients were evaluated. There were previous combination treatments of platinum and taxane regimens in 21 out of 27 patients, with 17 patients treated with carboplatin and paclitaxel and 4 patients treated with cisplatin or carboplatin and docetaxel. A total of 87 cycles was administered and the median number of cycles administered per patient was 3.5 cycles. Objective responses were observed in 5 out of 27 patients (18.5%). No severe hematologic and non-hematologic toxicities were observed (grade 3 leukopenia in 3 patients; grade 3 anemia in 3 patients; grade 3 thrombocytopenia in 2 patients; grade 3 diarrhea in 1 patient). The median survival time was 7.7 months and 1-year survival rate was 34.8%. CONCLUSION: Bi-weekly gemcitabine and irinotecan was well tolerated and had an acceptable response rate and a reasonable median survival time for patients with NSCLC who had previously been treated with platinum-based chemotherapy.     

Phase I study of irinotecan and gemcitabine in previously untreated patients with advanced non-small cell lung cancer

BACKGROUND: Irinotecan and gemcitabine are effective against non-small cell lung cancer. We conducted a phase I study of the combined use of irinotecan and gemcitabine in previously untreated patients with advanced non-small cell lung cancer to determine dose-limiting toxicities and maximum tolerated dose. METHODS: Patients were treated with irinotecan followed by gemcitabine on days 1 and 8 every 3 weeks. Gemcitabine dose was fixed at 1000 mg/m2, and irinotecan dose was increased from 60 mg/m2. RESULTS: A total of 16 patients was enrolled. Maximum tolerated dose of irinotecan was determined up to level 3 (irinotecan 100 mg/m2). In Japan, the maximum approved weekly dose of irinotecan is 100 mg/m2, so this was the dose that was used. Only very mild hematological and non-hematological toxicities were noted. CONCLUSION: Use of 100 mg/m2 irinotecan followed by 1000 mg/m2 gemcitabine on days 1 and 8 every 3 weeks warrants a phase II study.     

A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer

PURPOSE: To determine the maximum-tolerated dose (MTD) of irinotecan and paclitaxel in this two-drug combination, and to investigate a sequence-dependent effect in the pharmacokinetics of these drugs, we conducted a phase I study in chemo-na?ve patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were enrolled in this study. Both irinotecan and paclitaxel were administered on days 1 and 8, and repeated every 3 weeks. The starting dose of both drugs was 40 mg/m2 which was then alternately increased by 10 mg/m2 increments. In the first cycle, irinotecan was initially administered and followed by paclitaxel infusion, while the sequence of drug administration was reversed in the second cycle. Blood samples for pharmacokinetic analysis were obtained on day 1 of the first and second cycles. RESULTS: Nine patients received a total of 12 cycles, which were evaluated for toxicity and efficacy. The main hematological toxicity was neutropenia. Grades 3 or more neutropenia was observed in 67% of cycles at dose level 2. The main non-hematological toxicities were grade 3 febrile neutropenia, supraventricular arrhythmia, and grade 2 hepatic dysfunction. The MTD of irinotecan and paclitaxel were 40 and 50 mg/m2, respectively. In the pharmacokinetic analysis, the maximum concentration of paclitaxel was elevated in a dose-dependent manner. There was a trend toward elevation of the area under the plasma concentration-time curve (AUC) of irinotecan and a decline of the AUC of paclitaxel in cycle 1 (irinotecan followed by paclitaxel), compared with those in cycle 2 (paclitaxel followed by irinotecan). Hepatic toxicity was strongly associated with the AUC of irinotecan (r = 0.894, P < 0.0001). The objective response was not observed in the nine patients. CONCLUSION: The combination of irinotecan and paclitaxel with this schedule produced considerable toxicities without any antitumor effect for advanced NSCLC. The different schedule of administration or other combinations should be investigated.     

A phase I study of S-1 and irinotecan combination therapy in previously treated advanced non-small cell lung cancer patients

Background

This phase I study was conducted to evaluate the feasibility and to determine the recommended doses of the combination therapy of S-1 and irinotecan (CPT-11) in patients with advanced non-small cell lung cancer (NSCLC) as second-line treatment.

Methods

Patients with NSCLC who were previously treated with one chemotherapy regimen and had a performance status of 0 or 1 were eligible. CPT-11 was administered at 60 mg/m² (level 1), 80 mg/m² (level 2) on days 1 and 8, and oral S-1 was administered at 80 mg/day for body surface area (BSA) less than 1.25 m², 100 mg/day for BSA 1.25–1.5 m², and 120 mg/day for BSA more than 1.5 m² on days 1–14 every 3 weeks. The dose-limiting toxicity (DLT) was defined as grade 4 leukocytopenia or neutropenia, grade ≥3 neutropenia with fever over 38°C, grade ≥3 thrombocytopenia, or grade ≥3 major nonhematological toxicities.

Results

Nine patients were enrolled in the study. None of 3 patients enrolled in level 1 had any DLT. Of 6 patients in level 2, 2 patients had grade 3 diarrhea and one had grade 3 interstitial pneumonia. Level 1 was declared as the recommended dose.

Conclusion

The feasibility of the combination therapy of S-1 and CPT-11 was shown in the second-line setting for the treatment of advanced NSCLC. The recommended dose of CPT-11 was 60 mg/m² combined with standard dose of S-1 for phase II trials of pretreated advanced NSCLC patients.     

Phase I study of combination chemotherapy with gemcitabine and irinotecan for non-small cell lung cancer

A phase I study combining a fixed dose of gemcitabine with differing doses of CPT-11 every two weeks for previously treated non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A total of 21 patients with previously treated non-small cell lung cancer were treated every two weeks with CPT-11 followed by gemcitabine. The gemcitabine dose was fixed at 1000 mg/m2. The starting dose of CPT-11 (50 mg/m2) was then escalated different patients in 25 mg/m2 increments until 150 mg/m2 (level 5), the recommended dose as a single agent in Japan. RESULTS: Dose-limiting toxicity was only observed at level 5, in three of nine patients receiving the highest dose of CPT-11. One patient had grade 3 diarrhea, and two could not continue chemotherapy with grade 1 diarrhea or grade 1 neutropenia on day 15. Hematologic toxicity with this combination regimen, however, was generally mild. No grade 4 neutropenia, and only one case of grade 3 leukopenia was noted at level 5. Compliance with the combination regimen was good and there was no cumulative toxicity with the subsequent courses. Twenty-five courses of therapy were given at level 5 and the percentage of actual delivered doses/planned doses was 82%. CONCLUSIONS: The combination chemotherapy has only very mild toxicity and dose which can be recommended with this regimen are 1000 mg/m2 for gemcitabine and 150 mg/m2 for CPT-11 every two weeks.     

Phase I/II study of S-1 combined with biweekly irinotecan chemotherapy in previously treated advanced non-small cell lung cancer

Purpose

This phase I/II study was designed to evaluate a combination of irinotecan and S-1 a new regimen for salvage chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC).

Methods

The study group comprised patients with advanced or metastatic NSCLC who had previously received at least one platinum-containing chemotherapy. Patients received irinotecan on days 1, 15 and oral S-1 (40?mg/m² twice daily as a fixed dose) on day 1 to 14 of a 28-day cycle.

Results

In the phase I part, irinotecan was given in escalating doses of 70 (Level 1), 80 (Level 2), and 90?mg/m² (Level 3). Three of the 5 patients given Level 3 had dose-limiting toxicity, and Level 2 (80?mg/m² of irinotecan) was designated as the recommended dose. In phase II, 38 patients received a median of 7.4 cycles of irinotecan at the recommended dose. The overall response rate was 15.8?% (90?% confidence interval (CI): 6.1–25.5?%), and the median progression-free and overall survival times were 4.5?months (95?% CI: 3.5–5.0) and 15.0?months (95?% CI: 9.5–20.6) months, respectively. Toxicity was generally mild. Grade 3 or higher toxicity included neutropenia in 17.9?% of the patients, thrombocytopenia in 5.1?% and nausea in 7.7?%.

Conclusion

Combination chemotherapy with S-1 and irinotecan was considered an effective salvage regimen in patients with advanced or metastatic NSCLC.     

A phase II pharmacodynamic study of erlotinib in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy

PURPOSE: To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non-small cell lung cancer patients refractory to platinum-based chemotherapy. EXPERIMENTAL DESIGN: Patients were given erlotinib (150 mg/d). Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks' treatment. RESULTS: Of 73 evaluable patients, 7 (10%) had partial response and 28 (38%) had stable disease. In 53 patients with baseline tumor samples, no relationship was observed between pretreatment levels of EGFR, phosphorylated (p)-EGFR, p-AKT, p-mitogen-activated protein kinase (MAPK), or p27 and clinical benefit (i.e., response, or stable disease >/=12 weeks). Tumors from 15 of 57 patients had high EGFR gene copy number, assessed using fluorescence in situ hybridization (FISH positive), 10 of whom had clinical benefit, compared with 5 of 42 FISH-negative patients. FISH-positive patients had longer median progression-free [137 versus 43 days, P = 0.002; hazard ratio (HR), 0.37] and overall (226 versus 106 days, P = 0.267; HR, 0.70) survival than FISH-negative patients. In paired biopsy samples from 14 patients, p-EGFR (P = 0.002), p-MAPK (P = 0.001), and Ki-67 (P = 0.025) levels were significantly reduced after 6 weeks' treatment. Apoptosis was significantly increased in patients with clinical benefit (P = 0.029), and may be a marker of clinical benefit. CONCLUSION: In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.     

A multicenter phase II study of the combination of irinotecan and gemcitabine in previously treated patients with small-cell lung cancer

OBJECTIVE: To evaluate efficacy and toxicity of the combination of irinotecan and gemcitabine in pretreated patients having small-cell lung cancer. PATIENTS AND METHODS: Thirty-one patients (median age 60 years, performance status 0-1 in 87% and 2 in 13% of the patients) with limited or extensive-stage disease, refractory or relapsing after at least one prior chemotherapy regimen, received gemcitabine 1,000 mg/m(2) on days 1 and 8 and irinotecan 300 mg/m(2) on day 8, every 21 days. Sixteen (52%) patients had sensitive and 15 (48%) refractory disease. Fifteen patients (48%) had received > or =2 prior regimens. RESULTS: All patients were evaluable for toxicity and 26 for response analysis. A median of three (range 1-6) cycles per patient was administered. Three partial responses were documented for an overall response rate of 10% (95% CI 0.73-20.09), and disease stabilization was obtained in 7 patients (22%; intention-to-treat analysis). Two of the responders had refractory, and 1 had sensitive disease. The median time to progression was 4.5 months, the median duration of responses was 2.5 months, and the median survival time was 6 months. Grade 3-4 (WHO) neutropenia was observed in 9 patients (29%), grade 3-4 thrombocytopenia in 4 (13%), and grade 3-4 diahrrea in 3 patients (10%). Three patients experienced febrile neutropenia. No toxic deaths occurred. CONCLUSIONS: The combination showed modest activity in this patient group with a poor prognosis. Thus we believe it merits further investigation in the treatment of patients with small-cell lung cancer who have failed one prior chemotherapy regimen.     

A Phase II NCCTG study of irinotecan and docetaxel in previously treated patients with non-small cell lung cancer

Purpose: This Phase II study was undertaken to define the efficacy and toxicity of the combination of docetaxel and irinotecan for the second-line treatment of non-small cell lung cancer (NSCLC). Patients and Methods: Forty-six patients with measurable NSCLC who had relapsed after an initial response to chemotherapy or who had failed to respond to initial chemotherapy, received 130 mg/m² of irinotecan IV over 90 minutes and 50 mg/m² docetaxel IV over 60 minutes on Day 1 q3 weeks for 6 cycles. Dexamethasone and diphenhydramine pretreatment were given. Response to treatment was evaluated by response evaluation criteria in solid tumors RECIST criteria, and toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 2.0. Results: The most common severe (NCI CTC Grade 3+) adverse events were neutropenia (67 percent), diarrhea (28 percent), fatigue (20 percent), nausea (17 percent), infection (15 percent), vomiting (13 percent), leucopenia (13 percent), abdominal pain (11 percent), and dyspnea (11 percent). Grade 5 toxic events were seen in 2 patients. One of these 2 cases was a possibly-treatment related event (intestinal fistula). The median number of treatment cycles received was 3. Twelve patients (26 percent) received all 6 cycles of treatment. Five patients (11 percent) had a confirmed response (complete response (CR), partial response (PR), or regression). Median follow-up for the five surviving patients is 26.5 months (range: 25.1-28.4). Forty-two patients have reported progressive disease and 41 patients have died. Median time-to-progression (TTP) and survival are 2.6 months and 7.5 months, respectively. Conclusion: This second-line treatment regimen of irinotecan and docetaxel in NSCLC patients has shown activity, but can not be recommended over single-agent regimens because of significant toxicity.     

贝伐单抗联合化疗治疗晚期多程治疗失败后的非小细胞肺癌临床观察

背景与目的:晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者多程治疗失败后,目前尚无标准的化疗方案。本研究旨在观察贝伐单抗联合化疗治疗晚期NSCLC多程治疗失败后的疗效和安全性。方法:2010年1月—2011年2月经病理证实符合入选标准的35例晚期NSCLC患者,接受贝伐单抗联合化疗方案治疗。化疗2个周期后按照实体瘤疗效评价标准(RECIST 1.0)评价疗效。按照美国国立癌症研究所制定的通用药物毒性标准3.0版评价不良反应。结果:35例患者中,30例完成2个周期以上的化疗,32例病例可评价疗效,总体PR 7例,SD 18例,PD 7例,RR为21.9%(7/32),DCR为78.1%(25/32);中位PFS为3个月,中位OS为8个月。与贝伐单抗相关的不良反应以高血压、蛋白尿和出血多见,其中多为Ⅰ、Ⅱ级,Ⅲ、Ⅳ级少见。结论:贝伐单抗联合化疗对晚期多程治疗失败后的NSCLC有一定的抗肿瘤活性和较高的疾病控制率,安全性较高,临床受益率高,是一种有临床应用前景的治疗方法。     

A phase I study of gemcitabine and irinotecan as second line treatment for advanced non-small cell lung cancer

A phase I study was conducted to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of gemcitabine and irinotecan combination therapy as second line treatment in patients with advanced non-small cell lung cancer (NSCLC). Twelve patients with measurable NSCLC (age range 46-74 years; 7 males, 5 females; performance status 0 = 4, 1 = 8) who progressed or failed first-line chemotherapy were enrolled. Prior chemotherapy was platinum-based without gemcitabine or irinotecan. Gemcitabine was administered at a fixed dose of 1,000 mg/m2 after irinotecan administration, and irinotecan was administered at doses from 50 to 125 mg/m2 with an increment of 25 mg/m2, both on day 1 and 8. Chemotherapy was repeated every 3 weeks. Grade 3/4 leukopenia occurred in three patients (25%), neutropenia in four (33%), anemia in one (8%), and thrombocytopenia in one (8%). Grade 3 nausea and vomiting was observed in three (25%), grade 2 diarrhea in one (8%), and liver dysfunction in one (8%). Other toxicities were mild. Two of the three patients at level 4 (irinotecan 125 mg/m2) experienced dose limiting toxicity: one patient experienced grade 4 leukopenia and neutropenia, and the other experienced treatment delay of more than 2 weeks. The objective response rate was 16.6% (2/12). The maximum tolerated dose in this combination therapy was gemcitabine 1,000 mg/m2 and irinotecan 125 mg/m2. The dose level of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 on day 1 and 8 of a 3-week cycle is recommended for a phase II study.     

Second-line docetaxel and gemcitabine combination chemotherapy in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy

Docetaxel has been the only single active agent against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to evaluate the efficacy and safety of docetaxel combined with gemcitabine, another effective drug, in patients with NSCLC previously treated with platinum-based chemotherapy. Thirty-three patients were enrolled. Prior chemotherapy was cisplatin combined with etoposide in 24 patients and vinorelbine in 9 patients. Tumors were sensitive (n=15), resistant (n=9), and refractory (n=9) to front-line chemotherapy. Treatment was docetaxel 85 mg/m² on d 1, and gemcitabine 1200 mg/m² on d 1 and 8, with cycles repeated every three weeks. Ten patients (30.3%, 95% CI: 15.6–48.7) achieved a partial response and 15 (45.5%) stable disease. Responses were similar frequencies in platinum-sensitive and platinum-resistant/refractory tumors. With a median follow-up period of 5.7 mo (range 1.6–20.0), the median and 6-mo event-free survival were 5.5 mo, 40.6%, respectively. Median and 6-mo over-all survival were 7.3 mo and 52.7%. Patients with progressive disease to chemotherapy (p=0.0008), higher LDH (p=0.005), and NSE levels (p=0.03) survived shorter than other patients. In patients refractory to prior chemotherapy, survival was poor as borderline significantly (p=0.06). The major hematological toxicity was neutropenia. Grade III–IV neutropenia was noted in 14 (42%) patients, with three episodes of febrile neutropenia in 111 cycles. Docetaxel combined with gemcitabine is an active and safe second-line therapy for patients with NSCLC.     

Phase I study of vinorelbine and irinotecan in previously untreated patients with advanced non-small cell lung cancer

Introduction Vinorelbine alone and irinotecan alone have been shown to have efficacy against non-small cell lung cancer (NSCLC); each drug has different mechanisms of action. A phase I study using a combination of vinorelbine and irinotecan as first-line treatment for advanced NSCLC was done to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Methods Previously untreated patients (≤75 years old) with Stage IIIB or IV NSCLC were enrolled. Based on a 4-week cycle, vinorelbine was given on days 1 and 8, and irinotecan was given on days 1, 8, and 15 intravenously. To prevent an injection site reaction to vinorelbine, the site was treated with topical clobetasol ointment, and the patients were given intravenous dexamethasone prior to vinorelbine treatment. DLT was defined as grade 4 neutropenia lasting ≥4 days or febrile neutropenia, grade 4 thrombocytopenia, ≥grade 3 non-hematological toxicities, or the need to cancel drug administration on both days 8 and 15. Results A total of 23 patients were enrolled. DLT was observed in 1 of 6 patients at level 3 (20 mg/m² vinorelbine, 50 mg/m² irinotecan), in 2 of 3 at level 4 (25 mg/m², 50 mg/m²), and in 2 of 5 at modified level 4 (20, 60 mg/m²). Level 4 and modified level 4 were considered to be the MTD; dose level 3 was therefore recommended. DLTs included liver dysfunction, pneumonitis, colitis, and arrhythmia. Injection site reactions were mild. Hematological and non-hematological toxicities were mild and easily controlled. Conclusion Use of 20 mg/m² vinorelbine on days 1 and 8 followed by 50 mg/m² irinotecan on days 1, 8, and 15 every 4 weeks warrants a phase II study.     

A phase I study of combination chemotherapy with gemcitabine and oral UFT for advanced non-small cell lung cancer

A phase I study was carried out to determine the optimal dose and administration schedule for combined UFT plus gemcitabine therapy in patients with non-small cell lung cancer. Twenty-four patients (including 11 patients previously treated with cisplatin as the key drug) received oral UFT 400 mg x m(-2) on days 1 to 14 with intravenous infusions of gemcitabine (800 mg x m(-2) on days 8 and 15, or 900 mg x m(-2) on days 8 and 15, or 900 mg x m(-2) on days 1, 8 and 15). The most appropriate dosing option appeared to be 400 mg x m(-2) per day of oral UFT for 14 consecutive days with 900 mg x m(-2) gemcitabine on days 8 and 15. Eight of the 24 patients achieved partial response. The combination chemotherapy UFT and gemcitabine was well tolerated and may benefit patients with advanced non-small cell lung cancer. A multicentre phase II study using a 3-weekly regimen is in progress.     

Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

Background  

The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC.