Front-line paclitaxel and irinotecan combination chemotherapy in advanced non-small-cell lung cancer: a phase I-II trial

Our purpose was to determine the efficacy of irinotecan plus paclitaxel administered on day 1, repeated every 2 weeks, in untreated patients with advanced or metastatic non-small-cell lung cancer (NSCLC). In total, 56 patients with inoperable or metastatic stage III and IV NSCLC with a histologically or cytologically confirmed diagnosis were enrolled. None of the patients had undergone prior chemotherapy or radiation therapy. Treatment involved irinotecan 125 mg m(-2) and paclitaxel 135 mg m(-2) administered on day 1 and repeated every 2 weeks for a planned number of nine cycles. With a standard dose of paclitaxel at 135 mg m(-2), the dosage of irinotecan was escalated at four levels: 75, 100, 125 and 150 mg m(-2); 125 mg m(-2) was established as the maximum tolerated dose; this dosage was administered to 46 patients. A total of 52 patients (median age 65 years, range 38-77 years) were assessable for toxicity and survival and 46 for response rate. Out of 46 evaluable patients, 19 achieved partial response (41.3%), 17 had stable disease (37%) and 10 (21.7%) experienced disease progression. The median duration of response was 6 months (range 2-9+ months). The main adverse reactions were myelotoxicity (grades 3 and 4) in 10 (19.2%) patients and diarrhoea (grade 3) in four (7.7%) patients. Irinotecan combined with paclitaxel, administered every 2 weeks, appears to be an effective treatment for advanced-stage NSCLC.     

Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan.

BACKGROUND: To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan (IP) in patients with untreated advanced non-small-cell lung cancer (NSCLC) by a non-inferiority design. PATIENTS AND METHODS: A total of 602 patients were randomly assigned to one of four regimens: cisplatin 80 mg/m(2) on day 1 plus irinotecan 60 mg/m(2) on days 1, 8, 15 every 4 weeks (IP) carboplatin AUC 6.0 min x mg/mL (area under the concentration-time curve) on day 1 plus paclitaxel 200 mg/m(2) on day 1 every 3 weeks (TC); cisplatin 80 mg/m(2) on day 1 plus gemcitabine 1000 mg/m(2) on days 1, 8 every 3 weeks (GP); and cisplatin 80 mg/m(2) on day 1 plus vinorelbine 25 mg/m(2) on days 1, 8 every 3 weeks (NP). RESULTS: The response rate, median survival time, and 1-year survival rate were 31.0%, 13.9 months, 59.2%, respectively, in IP; 32.4%, 12.3 months, 51.0% in TC; 30.1%, 14.0 months, 59.6% in GP; and 33.1%, 11.4 months, 48.3% in NP. No statistically significant differences were found in response rate or overall survival, but the non-inferiority of none of the experimental regimens could be confirmed. All the four regimens were well tolerated. CONCLUSION: The four regimens have similar efficacy and different toxicity profiles, and they can be used to treat advanced NSCLC patients.     

Phase II study of cisplatin,ifosfamide, and irinotecan with rhG-CSF support in patients with stage IIIb and IV non-small-cell lung cancer

A phase II study of cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony stimulating factor (rhG-CSF) support was conducted in previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). Between June 1998 and August 2001, 50 patients were registered in this phase II study. Cisplatin (20 mg m(-2)) and ifosfamide (1.5 g m(-2)) were administered on days 1-4 and irinotecan (60 mg m(-2)) was given on days 1, 8, and 15, respectively. This regimen was repeated every 4 weeks. rhG-CSF was administered subcutaneously at a dose of 50 microg m(-2) on days 5-18 except on the days of irinotecan treatment. In total, 49 patients were assessable for toxicity and response and 50 for survival. In all, 33, patients (67.3%; 95% confidence interval 57.4-77.2%) achieved an objective response. The median response duration was 192 days and the median time to progression for 49 patients was 170 days. The median survival time was 540 days with 1- and 2-year survival rates of 63.5 and 30.7%, respectively. Grade 3 or 4 neutropenia and thrombocytopenia developed in 63.3 and 38.8% of the patients, respectively. In conclusion, the combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support was highly effective for the treatment of stage IIIB or IV NSCLC with acceptable toxicities.     

Fractionated administration of irinotecan and cisplatin for treatment of non-small-cell lung cancer: a phase II study of Okayama Lung Cancer Study Group.

A phase II study of fractionated administration of irinotecan (CPT-11) and cisplatin (CDDP) in patients with non-small-cell lung cancer (NSCLC) was conducted. Between January 1996 and January 1998, 44 previously untreated patients with stage IIIB or IV NSCLC were enrolled. CDDP at a dose of 60 mg x m(-2) was given first and followed by CPT-11 at a dose of 50 mg x m(-2). Both drugs were given by 1-hour infusion on days 1 and 8, and repeated every 4 weeks up to 4 cycles. 42 patients were evaluated for response and 44 for survival and toxicity. 20 patients (48%: 95% confidence interval 32-63%) achieved an objective response. The median duration of responses was 8 months, and the median survival time and the 1-year survival rate were 12.5 months and 56.8%, respectively. Major toxicities were neutropenia and diarrhoea. Grade 3 or 4 neutropenia occurred in 70.5% of the patients and one patient died of sepsis. Grade 3 or 4 diarrhoea was experienced in 25.0%, but manageable by conventional therapy. In conclusion, fractionated administration of CPT-11 and CDDP was highly effective for advanced NSCLC with manageable toxicities.     

A randomised phase II trial of docetaxel vs docetaxel and irinotecan in patients with stage IIIb-IV non-small-cell lung cancer who failed first-line treatment

Response rate and toxicity of second-line therapy with docetaxel (75 mg m(-2)) or docetaxel, irinotecan, and lenogastrim (60 mg m(-2), 200 mg m(-2), and 150 microg m(-2) day(-1), respectively) were compared in 108 patients with stage IIIb-IV non-small-cell lung cancer. Addition of irinotecan to docetaxel does not improve response rate, and increases gastrointestinal toxicity.     

Randomised phase II study of docetaxel/cisplatin vs docetaxel/irinotecan in advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group Study (WJTOG9803)

Docetaxel plus cisplatin and docetaxel plus irinotecan are active and well-tolerated chemotherapy regimens for advanced non-small-cell lung cancer (NSCLC). A randomised phase II study compared their efficacy and toxicity in 108 patients with stage IIIb/IV NSCLC, who were randomised to receive docetaxel 60 mg m(-2) and cisplatin 80 mg m(-2) on day 1 (DC; n=51), or docetaxel 60 mg m(-2) on day 8 and irinotecan 60 mg m(-2) on day 1 and 8 (DI; n=57) every 3 weeks. Response rates were 37% for DC and 32% for DI patients. Median survival times and 1- and 2-year survival rates were 50 weeks (95% confidence interval: 34-78 weeks), 47 and 25% for DC, and 46 weeks (95% confidence interval: 37-54 weeks), 40 and 18% for DI, respectively. The progression-free survival time was 20 weeks (95% confidence interval: 14-25 weeks) with DC and 18 (95% confidence interval: 12-22 weeks) with DI. Significantly more DI than DC patients had grade 4 leucopenia and neutropenia (P<0.01); more DC patients had grade >/=2 thrombocytopenia (P<0.01). Nausea and vomiting was more pronounced with DC (P<0.01); diarrhoea was more common with DI (P=0.01). Three treatment-related deaths occurred in DC patients. In conclusion, although the DI and DC regimens had different toxicity profiles, there was no significant difference in survival.     

吉西他滨联合顺铂治疗晚期非小细胞肺癌的临床观察

目的：总结西宁地区（海拔2260m）盐酸吉西他滨联合顺铂化疗方案治疗晚期非小细胞肺癌（NSCLC）的疗效及不良反应。方法：我科30例Ⅲ、Ⅳ期非小细胞肺癌患者，应用GP方案盐酸吉西他滨t250mg／m2（d，8）于60rain内静脉滴注，顺铂30mg／m2（d1-2）静脉滴注，21d为1周期，治疗2个周期后评价疗效。结果：CR0例，PR14例，sD8例，PD8例，总有效率（PR＋CR）为46．7％（14／30）；不良反应为白细胞、血小板下降和恶心、呕吐，但均可耐受。结论：高海拔地区应用盐酸吉西他滨联合顺铂方案，治疗晚期非小细胞肺癌有较好的疗效，且不良反应可以耐受。     

Randomised phase II trial of irinotecan plus cisplatin vs irinotecan, cisplatin plus etoposide repeated every 3 weeks in patients with extensive-disease small-cell lung cancer

Patients with previously untreated extensive-disease small-cell lung cancer were treated with irinotecan 60 mg m(-2) on days 1 and 8 and cisplatin 60 mg m(-2) on day 1 with (n=55) or without (n=54) etoposide 50 mg m(-2) on days 1-3 with granulocyte colony-stimulating factor support repeated every 3 weeks for four cycles. The triplet regimen was too toxic to be considered for further studies.     

A phase I/II trial of irinotecan-cisplatin combined with an anti-late-diarrhoeal programme to evaluate the safety and antitumour response of this combination therapy in patients with advanced non-small-cell lung cancer

We conducted a phase I/II study in patients with advanced non-small-cell lung cancer (NSCLC) to increase the therapeutic index of the cisplatin-irinotecan combination by institution of an anti-late-diarrhoeal program (ADP). A total of 77 chemotherapy-naive patients with advanced NSCLC were enrolled. The cisplatin dose was fixed at 60 mg m(-2) (Day 1). Irinotecan was escalated in 5 mg m(-2) increments, starting from 60 mg m(-2) (Days 1 and 8). ADP consisted of oral sodium bicarbonate, magnesium oxide, basic water, and ursodeoxycholic acid, and was administered orally for 4 days with each dose of irinotecan. In the phase I portion, irinotecan pharmacokinetics was also examined. After the recommended dose of irinotecan with ADP was determined, a phase II study was conducted to evaluate the response. Maximum tolerated dose was reached at an irinotecan dose of 80 mg m(-2) (Grade 4 diarrhoea and neutropenia). Pharmacokinetic studies show that the maximum concentration and the area under the curve of both irinotecan and SN38 (active metabolite of irinotecan) tend to increase in the dose-dependent manner of irinotecan. The phase II portion of the study included 48 patients, who were treated with 75 mg m(-2) of irinotecan. Grade 3/4 toxicities included neutropenia in 65%, leucopenia in 33%, and late diarrhoea in 6% of the patients. During this treatment, PS did not change in 65% of patients. At the end of the chemotherapy, PS did not decline in 90% of patients. In the phase II portion, a response occurred in 63% (95% confidential interval (CI), 47-76%) of patients. Median time to progression was 19 weeks (95% CI, 15-22 weeks), and median survival was 52 weeks (95% CI, 39-64 weeks). This regimen of irinotecan and cisplatin with ADP resulted in promising efficacy with acceptable toxicity for patients with advanced NSCLC. This regimen is a candidate for the experimental arm towards future phase III studies.     

A randomised phase III trial comparing consolidation treatment with further chemotherapy to chest irradiation in patients with initially unresectable locoregional non-small-cell lung cancer responding to induction chemotherapy

Purpose: A phase III randomised trial was conducted in patients with non-metastatic unresectable non-small-cell lung cancer in order to compare, in responders to induction chemotherapy, consolidation treatment by further chemotherapy to chest irradiation.Patients and methods: A total of 462 untreated NSCLC patients were eligible for three courses of induction chemotherapy (MIP) consisting of cisplatin (50 mg/m2), ifosfamide (3 g/m2) and mitomycin C (6 mg/m2). It was proposed that objective responders be randomised to either three further courses of MIP or to chest irradiation (60 Gy; 2 Gy per fraction given over six weeks).Results: An objective response rate of 35% was achieved; 115 patients (including 52% with initial stage IIIA and 44% with initial stage IIIB) were randomised to consolidation treatment, 60 of them to further chemotherapy and 55 to chest radiotherapy. There was no significant difference in survival between the two arms, with a respective median and two-year survival of 42 weeks (95% confidence intervals (95% CI): 35–51) and 18% (95% CI: 8–28) for chemotherapy and 54 weeks (95% CI: 43–73) and 22% (95% CI: 11–33) for irradiation. There was also no statistical difference for response duration between the two arms but chest irradiation was associated with a significantly greater duration of local control than chemotherapy (median duration times: 158 vs. 31 weeks, P = 0.0007).Conclusions: For non-metastatic unresectable NSCLC treated by an induction chemotherapy regimen containing cisplatin and ifosfamide, if an objective response is obtained, consolidation treatments by further chemotherapy or by chest irradiation result in non-statistically different survival distributions, although a better local control duration is observed with radiotherapy.     

Multicenter phase II trial of Genexol-PM, a novel Cremophor-free, polymeric micelle formulation of paclitaxel, with cisplatin in patients with advanced non-small-cell lung cancer.

BACKGROUND: Genexol-PM is a novel Cremophor EL (CrEL)-free polymeric micelle formulation of paclitaxel (Taxol). This multicenter phase II study was designed to evaluate the efficacy and safety of the combination of Genexol-PM and cisplatin for the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC received Genexol-PM 230 mg/m(2) and cisplatin 60 mg/m(2) on day 1 of a 3-week cycle as first-line therapy. Intrapatient dose escalation of Genexol-PM to 300 mg/m(2) was carried out from the second cycle if the prespecified toxic effects were not observed after the first cycle. RESULTS: Sixty-nine patients were enrolled in this study. Overall response rate was 37.7%. The median time to progression was 5.8 months and the median survival period was 21.7 months. The major non-hematologic toxic effects included grade 3 peripheral sensory neuropathy (13.0%) and grade 3/4 arthralgia (7.3%). Four patients (5.8%) experienced grade 3/4 hypersensitivity reactions. The major hematological toxic effects were grade 3/4 neutropenia (29.0% and 17.4%, respectively). CONCLUSION: Genexol-PM plus cisplatin combination chemotherapy showed significant antitumor activity. The use of CrEL-free, polymeric micelle formulation of paclitaxel allowed administration of higher doses of paclitaxel compared with the CrEL-based formulation without significant increased toxicity.     

Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: Results from a British Thoracic Oncology Group randomised phase III trial

BackgroundPlatinum-based combination chemotherapy is standard treatment for the majority of patients with advanced non-small-cell lung cancer (NSCLC). The trial investigates the importance of the choice of platinum agent and dose of cisplatin in relation to patient outcomes.MethodsThe three-arm randomised phase III trial assigned patients with chemo-naïve stage IIIB/IV NSCLC in a 1:1:1 ratio to receive gemcitabine 1250 mg/m² on days 1 and 8 of a 3-week cycle with cisplatin 80 mg/m² (GC80) or cisplatin 50 mg/m² (GC50) or carboplatin AUC6 (GCb6) for a maximum of four cycles. Primary outcome measure was survival time, aiming to test for a difference between treatment arms and also assess non-inferiority with pre-defined margin selected as hazard ratio (HR) of 1.2. Secondary outcome measures included response rate, adverse events and quality of life (QoL).FindingsThe trial recruited 1363 patients. Survival time differed significantly across the three treatment arms (p = 0.046) with GC50 worst with median 8.2 months compared to 9.5 for GC80 and 10.0 for GCb6. HRs (adjusted) for GC50 compared to GC80 was 1.13 (95% confidence interval [CI] 0.99–1.29) and for GC50 compared to GCb6 was 1.23 (95% CI: 1.08–1.41). GCb6 was significantly non-inferior to GC80 (HR = 0.93, upper limit of one-sided 95% CI 1.04). Adjusting for QoL did not change the findings. Best objective response rates were 29% (GC80), 20% (GC50) and 27% (GCb6), p < 0.007. There were more dose reductions and treatment delays in the GCb6 arm and more adverse events (60% with at least one grade 3–4 compared to 43% GC80 and 30% GC50).InterpretationIn combination with gemcitabine, carboplatin at AUC6 is not inferior to cisplatin at 80 mg/m² in terms of survival. Carboplatin was associated with more adverse events and not with better quality of life. Cisplatin at the lower dose of 50 mg/m² has worse survival which is not compensated by better quality of life.ClinicalTrials.gov identifierNCT00112710.EudraCT Number2004-003868-30.Cancer Research UK trial identifierCRUK/04/009.     

紫杉醇持续输注联合顺铂治疗晚期非小细胞肺癌

背景与目的：在许多国家肺癌的发病率和死亡率急剧增长，治疗肺癌的药物和方法不断涌现。本研究探讨紫杉醇静脉持续注射联合顺铂治疗晚期非小细胞肺癌的疗效和毒性。方法：61例晚期非小细胞肺癌患者被随机分为两组，治疗组（31例）方案：紫杉醇按总量150mg／m^2 48h静脉持续输注，第1～2天；顺铂按总量75mg／m^2分3d静点，即第3、4、5天。对照组（30例）方案：紫杉醇按总量150mg／m^2分2次静点，即第1、8天，每次持续3h，顺铂用法同治疗组。所有患者每周期21d，每个患者治疗3个周期以上。结果：治疗组与对照组的近期有效率分别为54．84％（17／31）、43．33％（13／30），中位治疗进展时间7．1个月、5．8个月，中位生存时间（MST）14．0个月、10．2个月，1年生存率67．74％（21／31）、33．33％（10／30），2年生存率22．58（7／31）％、13．33％（4／30），其中1年生存率治疗组显著高于对照组（P〈0．05），其余差异均无显著性（P〉0．05）。两组患者的不良反应有：骨髓抑制、恶心呕吐、脱发、外周神经毒性、肝功异常、肾功异常、静脉炎，两组发生率相当。结论：较传统用法，紫杉醇持续输注治疗晚期非小细胞肺癌能够提高有效率，显著改善生存情况。毒副反应无明显增加。     

Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin.

BACKGROUND: This multicenter, randomized, phase III study compared the efficacy, including progression-free survival (PFS), and safety of gemcitabine-docetaxel (GD) combination versus cisplatin-vinorelbine (CV) in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemonaive patients with stage IIIB or IV NSCLC were treated with GD (gemcitabine 1000 mg/m(2) days 1 and 8 plus docetaxel 85 mg/m(2) day 8, every 3 weeks for eight cycles) or CV (cisplatin 100 mg/m(2) day 1 plus vinorelbine 30 mg/m(2), days 1, 8, 15 and 22, every 4 weeks for six cycles). RESULTS: A total of 311 patients were enrolled (155 GD and 156 CV). Neither PFS nor overall survival differed significantly between the two arms (median PFS 4.2 and 4 months; median survival 11.1 and 9.6 months; 1-year survival 46% and 42%, for GD and CV, respectively). For the GD arm compared with the CV arm, the hazard ratio for PFS was 1.04 [95% confidence interval (CI) 0.83-1.32], and for overall survival, it was 0.90 (95% CI 0.70-1.16). Objective response rates did not differ significantly (31% for GD, 35.9% for CV). Myelosupression, emesis and frequency of febrile neutropenia were less pronounced on the GD arm, whereas fluid retention and pulmonary events were more pronounced. The CV arm experienced a higher number of serious adverse events and a lower compliance with the protocol. There was no quality of life (QoL) difference between arms. Median time to definite impairment of health-related QoL was 153 and 168 days in GD and CV arms, respectively. CONCLUSIONS: There was no advantage in PFS with GD compared with CV; however, the CV regimen had higher rate of toxic events, mainly myelosuppression. The herein, non-platinum-containing regimen could be considered as a rational alternative to the cisplatin-based doublet.     

Vinorelbine-gemcitabine in advanced non-small-cell lung cancer (NSCLC): an AASLC phase II trial. Austrian Association for the Study of Lung Cancer.

Purpose:The purpose of the present phase II trial was todetermine the efficacy and toxicity of vinorelbine–gemcitabine inpatients with advanced non-small-cell lung cancer (NSCLC). Patients and methods:From December 1997 to February 1999, 78chemotherapy-naive patients (median age 60 years, Karnofsky performance statusof 100, 90, 80 and 70 present in 5%, 41%, 36% and18% of the patients, respectively) with stage IIIB (17%) or IV(83%) NSCLC (65% adenocarcinomas, 22% squamous-cellcarcinomas, 10% large-cell carcinomas, 3% mixed-cell carcinomas)received 25 mg/m² vinorelbine and 1200 mg/m² gemcitabineon days 1, 8 and 15 of a four-week cycle. Results:In an intent-to-treat analysis, partial responses wereseen in 19% of the patients. The median duration of response was 4.4months. The median survival time was seven months and the one-year survivalrate was 32%. Myelosuppression was the main side effect with WHO grade3/4 neutropenia and thrombocytopenia in 35% and 11% of thepatients, respectively. Other side effects were usually mild to moderate. Conclusions:Vinorelbine–gemcitabine is active, welltolerated and easy to administer on an outpatient basis in advanced NSCLC.Thus a randomized comparison of this combination with platinum-based protocolsis warranted in patients with advanced NSCLC.     

Phase II trial of S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer

Background:

To assess the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation for unresectable stage III non-small-cell lung cancer (NSCLC).

Methods:

Eligible patients were 20–74 years old and had histologically or cytologically confirmed NSCLC, a performance status of 0–1, and no prior chemotherapy. Patients were treated with cisplatin (60 mg m⁻² on day 1) and S-1 (orally at 40 mg m⁻² per dose, b.i.d., on days 1–14), with the treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy thoracic radiation dose was delivered in 30 fractions.

Results:

Of 50 patients, 48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI: 79.1–96.9%). This regimen was well tolerated. Common toxicities included grade 3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3 pneumonitis (5%). Median progression-free survival was 12.0 months and median overall survival was 33.1 months. The 1- and 2-year survival rates were 89.5 and 56%, respectively.

Conclusion:

This chemotherapy regimen with concomitant radiotherapy is a promising treatment for locally advanced NSCLC because of its high response rates, good survival rates, and mild toxicities.     

First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: A multicenter phase II study

Purpose: To evaluate the efficacy and safety of the docetaxel-cisplatin combination in patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods: Chemotherapy-naïve patients with histologically confirmed, measurable stage IIIB or IV NSCLC, a World Health Organization (WHO) performance status of 0–2 and adequate bone marrow, renal, hepatic and cardiac function were eligible for the study. Patients received docetaxel (100 mg/m²) as an one-hour infusion on day 1 and cisplatin (80 mg/m²) as a 30-min infusion with appropriate hydration on day 2. Granulocyte colony-stimulating factor (G-CSF; 150 µg/m² , SC) was given on days 3 to 13. Treatment was repeated every three weeks.Results: Fifty-three patients were enrolled (28 with stage IIIB and 25 with stage IV). One complete and 23 partial responses were observed (overall response rate (OR): 45%; 95% CI: 34.1%–61.8%). The response rate was 57% and 32% in patients with stages IIIB and IV disease (P = NS). The median time to progression was 36 weeks and the median survival 48 weeks; the one-year survival was 48%. Grade 3–4 neutropenia occurred in 23 patients, 15 of whom were hospitalized for neutropenic fever; two patients died of sepsis. Grade 2 neurotoxicity was observed in six patients and grade 3 in five patients; grade 3 fatigue occurred in seven patients, grade 3–4 mucositis in four patients and grade 3–4 diarrhea in six patients. Mild allergic reactions and oedema were observed in five and four patients, respectively. The median dose intensity was 30 mg/m² /week for docetaxel and 24 mg/m² /week for cisplatin, corresponding to 91% and 89% of the specified protocol doses, respectively.Conclusions: The docetaxel–cisplatin combination is an active regimen in advanced NSCLC, but hematologic toxicity remains high despite the prophylactic use of G-CSF.     

Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, Pemetrexed disodium, ALIMTATM) and cisplatin: A multicenter phase II trial

Background:To evaluate the activity of MTA plus cisplatin inchemotherapy-naïve patients with non-small cell lung cancer (NSCLC). Patients and methods:Thirty-six chemotherapy-naïve patientswith NSCLC received 500 mg/m² MTA plus 75 mg/m²cisplatin every 21 days, with 4 mg dexamethasone orally twice daily on the daybefore, of, and after MTA administration. Results:Median age was 58 years. WHO performance status was0–2. Eighteen patients each had stage IIIB and IV disease. Seventeenpatients each had squamous-cell and adenocarcinoma; two had undifferentiateddisease. Fourteen patients (39%; 95% confidence interval:23%–57%) showed partial response; seventeen (47%)had stable disease. Median survival was 10.9 months. Twenty-one patients(59%) experienced grade 3 or 4 granulocytopenia without fever orinfection. Five (14%) and six (17%) patients experienced grade3 anemia and grade 3 or 4 thrombocytopenia, respectively. Nonhematologicaltoxicities included grade 3 nausea in two patients (6%), and grade 3and 4 diarrhea in one patient (3%) each. One patient each experiencedgrade 4 ALT and grade 3 bilirubin and AST elevations. Conclusions:MTA plus cisplatin is well tolerated and activeagainst NSCLC. Further studies of this combination are warranted.     

Phase II trial of irinotecan, cisplatin and mitomycin for relapsed small cell lung cancer

There is no standard therapy for relapsed small cell lung cancer (rSCLC). We evaluated the efficacy and toxicity of a new triplet consisting of irinotecan (100 mg/m(2) Days 1 and 15 q28), cisplatin (40 mg/m(2) Days 1 and 15 q28) and mitomycin (6 mg/m(2) d1 q28) administered to a maximum of 6 cycles in individuals with rSCLC that had relapsed following first line treatment. Partial remissions were observed in 35% and progression in 30% of patients. Progression free survival measured 4.5 months (95% CI 0.8-8.2) and overall survival was 7.8 months (95% CI 5.3-10.3). QoL showed improvement in activity symptoms and stabilization of physical symptoms. As IPM was a well-tolerated regimen with activity in rSCLC, a phase III trial comparing this triplet with other regimens in this setting is warranted.