Low-dose weekly paclitaxel as second-line treatment for advanced non-small cell lung cancer: a phase II study

PURPOSE: To assess the activity and toxicity of low-dose weekly paclitaxel in patients with non-resectable or metastatic non-small cell lung cancer (NSCLC) and who had disease recurrence or failure with previous chemotherapy. PATIENTS AND METHODS: Forty patients with NSCLC previously treated with platinum-based chemotherapy received weekly paclitaxel 80 mg/m(2) as a 1 h infusion. The median age was 63 years (range 42-77 years); 25 patients had Eastern Cooperative Oncology Group performance status (PS) 1 and 15 had PS 2. Thirty-one patients had stage IV disease and nine stage III (eight stage IIIB and one stage IIIA). RESULTS: A total of 364 weeks of treatment were administered (median 8 weeks, range 2-17 weeks). There were no episodes of grade 3 or 4 haematological toxicities. Severe non-haematological toxicity was uncommon: grade 1-2 asthenia in 50%; grade 1-2 motor neuropathy in 45% and grade 3 in 10%; grade 1-2 sensory neuropathy in 62% of patients. Alopecia was mild. The overall response rate was 37.5% (95% CI, 23.9-55): 2 CR, 13 PR, 15 SD, 8 PD, 2 NE. Median overall survival was 9.7 months (95% CI, 6.5-12.8). Median time to progression was 5.4 months (95% CI, 1.8-8.9). CONCLUSION: A low-dose weekly paclitaxel regimen had good clinical efficacy with low toxicity in this group of patients with poor prognosis. This regimen increases the therapeutic options available for second-line therapy in NSCLC patients.     

Phase II study of weekly paclitaxel as second-line therapy in patients with advanced non-small cell lung cancer

A growing number of patients, mainly cisplatin-pretreated, require second-line therapy for non-small cell lung cancer (NSCLC) but the optimal treatment and appropriate criteria for patient selection have not been defined yet. A second-line phase II study was conducted in cisplatin-pretreated patients with advanced NSCLC to evaluate the activity and toxicity of weekly paclitaxel. Fifty-three consecutive NSCLC patients (9 stage IIIA-B, 44 stage IV) progressing after one front line cisplatin-based chemotherapy were enrolled. Previous treatment with taxanes was not allowed. Patients with stage III were also pretreated with thoracic radiotherapy. Weekly paclitaxel was administered as 1-h infusion at a dose of 80 mg/m(2) for three weeks with one week off, for a maximum of four courses. All patients were assessable for response, toxicity and survival. A complete response was observed in one case, partial response in 7, for an overall response rate (RR) of 15%, (95% Cl = 5-25%). Stable disease (SD) was registered in 11 patients, for an overall clinical benefit (CB = RR + SD) of 36% (95% Cl = 23-49%). Toxicity was mild, with G3-4 neutropenia and thrombocytopenia in 6 and 2% of patients, respectively. Non-hematological toxicities were negligible. No significant correlation between patient or treatment-related variable and RR was observed. CB was significantly higher in patients with non-squamous histology (P = 0.03) and no progression within 4 months of first line cisplatin-based chemotherapy (P = 0.007). Median progression-free survival (PFS) was 7 months in responders and 4 months in pts with SD. PFS was significantly related to good performance status (PS) (P = 0.002) and non-squamous histology (P = 0.004). In conclusion, weekly paclitaxel has acceptable palliative activity and excellent tolerance in cisplatin-pretreated patients. Patients with PS 0-1, non-squamous histology and with no progression within 4 months of first line cisplatin-based chemotherapy seem more likely to benefit from this treatment.     

Weekly docetaxel as second-line therapy in non-small cell lung cancer: a phase II study

INTRODUCTION: Single-agent docetaxel is active as second-line chemotherapy in non-small cell lung cancer (NSCLC) pretreated patients; seven phase II studies have shown response rates of about 20% and 9 months of median survival. Two phase III studies documented a survival benefit at 1 year compared to BSC and vinorelbine or ifosfamide. Recent trials indicate acceptable activity and a good safety profile of weekly docetaxel with doses of 25-43 mg/m2. The aim of our study was to confirm this evidence and to evaluate activity and toxicity of weekly docetaxel at the dose of 40 mg/m2. PATIENTS ATND METHODS: Twenty-one patients with NSCLC entered the study (7 stage IIIB and 14 stage IV): 13 males and 8 females. Median age was 66 years (range, 53-75). ECOG was O in 6, 1 in 9 and 2 in 6 patients. All patients were pretreated with a first-line chemotherapy (13 patients progressed soon after the first line); 6 of them received palliative radiotherapy on the chest. The treatment consisted of weekly docetaxel, 40 mg/m2 in 1 hr for six weeks with two weeks of rest (1 cycle). A total of 87 administrations was delivered (median, 4; range, 1-12). RESPONSES: All patients were assessable for response (according to the "intent-to-treat principle") and for toxicity. No complete or partial remission was observed; 2 minor responses (9.5%), 1 stable disease (5%), 8 progressive diseases (38%) were documented. Seven patients dropped out the study due to severe toxicity (33.5%) and 3 due to early death (14%). Median survival was 3 months (range, 1-17), and 1-year survival was 9.5%. Toxicity was as follows: grade 4 diarrhea in 1; grade 3 asthenia in 8 (38%), grade 3 stomatitis in 2; grade 3 neutropenia in 1; allergic reactions in 2. No treatment-related death was recorded. CONCLUSIONS: The trial showed only very modest activity of weekly docetaxel, with severe side effects that induced us to stop the accrual in order to prevent other worse toxicities. We therefore concluded that a dose of 40 mg/m2 of weekly docetaxel is not manageable and does not seem to provide a real benefit in terms of response and quality of life.     

A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer.

PURPOSE: Our aim was to evaluate the efficacy, toxicity, and pharmacokinetic behavior of single-agent paclitaxel given weekly to elderly patients with lung cancer. EXPERIMENTAL DESIGN: Previously untreated patients with stage IIIB/IV non-small cell lung cancer were eligible for the study if they were at least 70 years of age and had preserved organ function. Paclitaxel was administered over 1 h at a dose of 90 mg/m(2) for 6 consecutive weeks on an 8-week cycle. The pharmacokinetics of paclitaxel were assessed during the first and sixth week of therapy in a subgroup of eight patients. RESULTS: A total of 35 patients (median age, 76 years; range, 70-85) were enrolled. The overall response rate was 23%. Median time to failure was 5.2 months, whereas the median survival time was 10.3 months. Survival rates after 1 and 2 years were 45 and 22%, respectively. Grade 3/4 toxicities included neutropenia (5.8%), hyperglycemia (17.6%), neuropathy (5.8%), and infection (8.8%). Two patients died from treatment-related toxicity. There was no significant difference (P = 0.18) between the total body clearance of paclitaxel on the first (17.4 +/- 2.9 liters/h/m(2), mean +/- SD) and sixth (15.8 +/- 4.1 liters/h/m(2)) week of therapy. CONCLUSION: Paclitaxel administered as a weekly 1-h infusion at a dose of 90 mg/m(2) is a safe and effective therapy for elderly patients with advanced non-small cell lung cancer. Its pharmacokinetics in elderly patients do not appear to differ from historical data for younger patients, and there was no suggestion of a change in drug clearance after repeated weekly dosing.     

A multi-center phase II study of weekly topotecan as second-line therapy for small cell lung cancer

PURPOSE: To determine the response rate, toxicity, failure free and overall survival of weekly topotecan in patients with relapsed small cell lung cancer who received one prior platinum based chemotherapy. PATIENTS AND METHODS: Twenty two patients with relapsed disease after response to one prior chemotherapy with or without radiotherapy and patients with relapse more than 90 days after their last therapy received topotecan 4mg/m(2) intravenous over 30min on days 1,8,15; every 4 weeks (3 weeks on and 1 weeks off). Chemotherapy was given until disease progression or unacceptable toxicity. RESULTS: Of 22 patients, none of the patients responded to weekly topotecan therapy. Four patients had stable disease. After a median follow up of 1 year, median time to progression was 6 weeks and median survival was 5 months. The common toxicities associated with this regimen were anemia, thrombocytopenia, fatigue, GI side effects and alopecia. CONCLUSION: Weekly topotecan was well tolerated but ineffective in this trial. Although commonly used, weekly regimen of topotecan should be used with caution in relapsed SCLC.     

A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer

We conducted this phase II study to explore the efficacy and safety of weekly paclitaxel combined with carboplatin in elderly patients with advanced non-small cell lung cancer (NSCLC). Elderly patients (> or = 70 years old) of stage IIIB, IV, or recurrent NSCLC with PS 0 or 1 were enrolled. Patients received paclitaxel at a dose of 70 mg/m2 on Days 1, 8, 15, and carboplatin at the target dose of the area under the curve (AUC) of six on Day 1 every 28 days for at least two cycles. Forty-two patients were enrolled and 40 patients were treated with a median of three cycles (range, 1-5). The overall response rate (ORR) was 45% (95% confidence interval, 30-60%). The median survival time (MST) was 14 months and the 1-year survival rate was 62%. Twenty-eight patients (70%) had grade 3/4 neutropenia and two patients (5%) experienced grade 3 febrile neutropenia. Non-hematological toxicities were generally mild to moderate and grade 3 peripheral neuropathy was seen in one patient (3%). There was one treatment-related death by infection due to neutropenia. Weekly paclitaxel and carboplatin combination chemotherapy was an effective and safe regimen in elderly patients with advanced NSCLC. A randomized trial comparing this treatment with the conventional tri-weekly regimen of paclitaxel and carboplatin is warranted.     

Targeting cyclooxygenase-2 in recurrent non-small cell lung cancer: a phase II trial of celecoxib and docetaxel.

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in prostaglandin (PG) synthesis and is overexpressed in 70% to 90% of non-small cell lung cancers (NSCLC). Preclinical studies suggest inhibition of COX-2 can enhance the cytotoxic effect of docetaxel. To test this concept clinically, we administered celecoxib (400 mg p.o. twice daily) plus docetaxel (75 mg/m(2) every 3 weeks) to a cohort of patients with recurrent, previously treated NSCLC. Patients first received single agent celecoxib for 5 to 10 days to ascertain the effectiveness of COX-2 inhibition, which was determined by measuring pre- and post-celecoxib levels of urinary 11alpha-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), the major metabolite of prostaglandin E(2) (PGE(2)). We enrolled 56 patients (35 men, 21 women; median age, 61 years). All patients had received at least one prior chemotherapy regimen. The overall response rate was 11% and median survival was 6 months, similar to that observed with docetaxel alone. Pre-celecoxib urinary PGE-M decreased from a mean level of 27.2 to 12.2 ng/mg Cr after 5 to 10 days of celecoxib (P = 0.001). When grouped by quartile, patients with the greatest proportional decline in urinary PGE-M levels experienced a longer survival compared to those with no change or an increase in PGE-M (14.8 versus 6.3 versus 5.0 months). Our data suggest that combining celecoxib with docetaxel using the doses and schedule employed does not improve survival in unselected patients with recurrent, previously treated NSCLC. However, in light of the apparent survival prolongation in the subset with a marked decline in urinary PGE-M levels, further investigation of strategies designed to decrease PGE(2) synthesis in NSCLC seems warranted.     

Cisplatin and weekly docetaxel as first-line therapy in patients with advanced non-small cell lung cancer a phase II study

BACKGROUND: Based on the results of previous phase I studies, in the current phase II trial we evaluated the efficacy and toxicity of cisplatin plus weekly docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The eligibility criteria for the study included newly diagnosed stage IIIB/IV NSCLC, age < or = 75 years, Eastern Cooperative Oncology Group performance status of 0-2, adequate organ functions, and signed informed consent. The chemotherapy regimen consisted of cisplatin, 80 mg/m2 on day 1, and docetaxel, 25 mg/m2 on days 1, 8 and 15 every 4 weeks. RESULTS: Between January 2002 and December 2003, 31 patients with NSCLC were enrolled in the study. An objective response rate of 40% (95% CI, 21-60) was obtained in 27 assessable patients. The median time to progression was 6.4 months (range, 2.5-26.3) and median overall survival was 10.01 months (range, 5-28.3). The regimen was well tolerated with no grade 4 toxicity. CONCLUSIONS: Cisplatin plus weekly docetaxel is an effective and well-tolerated regimen in chemo-naive patients with advanced NSCLC. A phase III study of weekly versus the conventional regimen of every three weeks should be conducted to compare the survival benefits, toxicity profile and quality of life.     

Phase II study of weekly chemotherapy with paclitaxel and gemcitabine as second-line treatment for advanced non-small cell lung cancer after treatment with platinum-based chemotherapy

Purpose We evaluated the tolerability and activity of the combination of weekly paclitaxel (PTX) and gemcitabine (GEM) in second-line treatment of advanced non-small cell lung cancer (NSCLC) after treatment with platinum-based chemotherapy. Patients and methods PTX (100 mg/m²) and GEM (1,000 mg/m²) were administered to patients with previous treated NSCLC on days 1 and 8 every 3 weeks. Results A total of 40 patients (performance status 0/1/2, 7/27/6 pts) were enrolled. The response rate was 32.5% (95% confidence interval: 18.0–47.0%). The median survival time was 41.7 weeks (95% confidence interval: 28.5–54.7 weeks). The median time to disease progression was 19 weeks. Hematological toxicities (grade 3 or 4) observed included neutropenia in 60%, anemia in 15%, and thrombocytopenia in 12.5% of patients. Non-hematological toxicities were mild, with the exception of grade 3 diarrhea, pneumonitis, and rash in one patient each. There were no deaths due to toxicity. Conclusion The combination of weekly PTX and GEM is a feasible, well-tolerated, and active means of second-line treatment of advanced NSCLC.     

Cellular immune profile in patients with non-small cell lung cancer after weekly paclitaxel therapy

Paclitaxel is a new agent for advanced non-small cell lung cancer (NSCLC). Weekly doses may enhance antitumor activity while minimizing toxicity, but little is known about immune recovery. Paclitaxel (80 mg/m2) was administered to 10 patients with NSCLC, weekly during 3-week cycles. Natural killer (NK) activity, CD3-CD16+CD56+ NK cells, and differential counts were monitored. NK activity appeared in all patients after treatment with paclitaxel therapy NK activity showed a 27 +/- 9% decrease (mean +/- SE) on protocol day 8 and a 37 +/- 7% decrease on day 15 (p < 0.05) recovering to 89 +/- 5% of baseline on day 29. With weekly paclitaxel, a decrease in NK cell function persisted through the first cycle but then recovered. Weekly paclitaxel may be less immunosuppressive than agents such as cisplatin.     

The combination of carboplatin and weekly paclitaxel: a safe and active regimen in advanced non small-cell lung cancer patients. A phase I-II study

The combination of carboplatin and paclitaxel given every three weeks is a tolerated and reasonably active regimen in advanced non-small cell lung cancer (NSCLC). This study was designed to evaluate the maximum tolerated dose (MTD) of a fixed dose of carboplatin with an area under the curve (AUC) of 6 and escalating doses of weekly paclitaxel with an initial dose of 50 mg/m2 with 10 mg/m2 increments at each level in untreated NSCLC patients (phase I study). The study continued with a phase II study. Thirty patients entered the phase I study. The MTD was: carboplatin AUC = 6 on days 1 and 28 plus paclitaxel 100 mg/m2 (1 hour) on days 1, 8,15, 28. The dose-limiting toxicity (DLT) was severe neutropenia and cardiological toxicity. Subsequently, 42 patients entered the phase II study with the same treatment schedule. The 2-drug combination was globally well tolerated. The overall response rate (RR) was 42% [CI 95%: 26.3-57.7], stable disease (SD) 29% and progression (PD) 29%. The median duration of response was 8.0 mos (range: 1.0-19.0).The median time to progression was 8.0 mos (range: 7.0-19.0) and the median survival was 14.0 months (range: 9.0-19.0). The association of carboplatin AUC = 6 and weekly paclitaxel 100 mg/m2 proved to be manageable, active and extremely safe even in elderly patients (one third of all patients in our cohort). The survival results were interesting: the median survival time was 14 months (9-19 months) and the 1- and 2-year survival was 59% and 16%, respectively.     

Docetaxel and cyclooxygenase-2 inhibition with celecoxib for advanced non-small cell lung cancer progressing after platinum-based chemotherapy: a multicenter phase II trial

PURPOSE: To assess the overall and progression-free survival, response rate, and toxicity of combined docetaxel and celecoxib in the treatment of patients with non-small cell lung cancer progressing after initial chemotherapy for advanced disease. PATIENTS AND METHODS: Patients with non-small cell lung cancer and either measurable or evaluable disease experiencing progression after one or more platinum-based chemotherapy regimens given for advanced or metastatic disease, ECOG performance status 0-2, and adequate hematologic and biochemistry parameters were eligible for study inclusion; exclusion criteria included symptomatic brain metastases and full dose anti-coagulation. Therapy consisted of docetaxel 75 mg/m(2) every 21 days for a maximum of six cycles and celecoxib 400 mg orally twice daily commencing 7 days prior to docetaxel and continuing until disease progression. RESULTS: A total of 41 patients were enrolled of whom 39 were deemed eligible and received at least one course of docetaxel. The mean age of enrolled patients was 60.5 years (range, 44-77); 67% were men and 79% white. All but one patient had an Eastern Clinical Oncology Group (ECOG) performance status of 0 or 1. Most (72%) had been treated with a prior taxane. Overall survival was 11.3 months (95% confidence interval [CI]: 7.9, 15.7) and progression-free survival 19.6 weeks (95% CI: 13.5, 25.0). A response rate of 10.2% (95% CI: 3%, 24%) for all eligible and treated patients was found. Grade 3 or 4 neutropenia occurred in 10/39 patients (25.6%); one death due to neutropenic sepsis occurred. No grade 3 or 4 renal or hepatic toxicities were documented. CONCLUSION: Treatment with combination celecoxib and docetaxel is a safe regimen with a toxicity profile similar to that of docetaxel alone. Survival data are encouraging compared to historical controls and may prolong time to disease progression compared with single-agent docetaxel.     

Phase II study of carboplatin and weekly paclitaxel combination chemotherapy in advanced non-small cell lung cancer: a Kansai Clinical Oncology Group study

The objective of this phase II study was to evaluate the efficacy and toxicity of carboplatin and weekly paclitaxel combination chemotherapy in previously untreated, advanced non-small cell lung cancer (NSCLC). Patients received paclitaxel at a dose of 70 mg/m(2) on days 1, 8, 15, and carboplatin with the target dose of area under the curve (AUC) of 6 on day 1 every 28 days. Forty-six patients were enrolled. A median of four cycles (range, 1-13) were administered. Complete response was observed in one patient (2.2%) and partial response in 23 patients (50%), yielding an overall intent-to-treat response rate of 52.2% (95% confidence interval, 37.8-66.6%). The median survival time was 395 days and 1-year survival rate was 51.4%. Toxicities were mild. Twelve patients (26%) had grade 3 and three patients (7%) had grade 4 neutropenia. Grade 3 thrombocytopenia was seen in four patients (8%). Massive hematoemesis due to duodenal ulcer was observed in one patient, but no other patients experienced grade 3 or more non-hematological toxicities. There was no treatment-related death. Carboplatin and weekly paclitaxel combination chemotherapy is an efficacious and feasible regimen in patients with advanced NSCLC, and this treatment will be a reasonable alternative to the conventional triweekly regimen of paclitaxel and carboplatin.     

周剂量多西他赛联合顺铂二线治疗晚期非小细胞肺癌临床观察

目的观察多西他赛周剂量给药联合顺铂方案二线治疗晚期非小细胞肺癌（NSCLC）的临床疗效及毒副作用。方法2003年1月－2007年3月收治的54例既往治疗失败的ⅢB-Ⅳ期NSCLC患者,多西他赛35mg／m^2静脉点滴1小时,第1、8天,DDP25mg／m^2静脉点滴,第1～3天,21天为1个周期。结果54例中CR3例,PR9例,NC29例,PD13例。总有效率（RR）为22．3％（12／54）,临床获益率为76％。全组中位TTP为4个月（2—9个月）,中位生存期10月,1年生存率为39％,主要毒副作用为骨髓抑制,白细胞下降占64．8％（35／54）,达到Ⅲ～Ⅳ度的为9．3％（5／54）;非血液学毒副作用性轻微;全组无治疗相关性死亡。结论周剂量多西他赛联合顺铂方案二线治疗晚期非小细胞肺癌疗效较好,耐受性佳。     

A phase II study of weekly gemcitabine and paclitaxel in patients with previously untreated stage IIIb and IV non-small cell lung cancer

The purpose of this study was to determine the activity of paclitaxel as a second-line chemotherapy for non-small cell lung cancer (NSCLC). This multicentric trial included patients who had failed to a first-line chemotherapy with platinum derivatives and/or ifosfamide. After registration, patients were treated by paclitaxel i.v. at a dose of 225 mg/m(2) given over 3 h administered every 3 weeks. Response was assessed after three courses of therapy. Sixty-seven patients were registered, one was ineligible and 64 were assessable for response. Two partial responses were observed (3% of the eligible patients; 95% confidence interval: 0-7%). No change was documented in 16 cases (24%). Tolerance was acceptable, the main toxicity being cumulative polyneuropathy. Median survival duration was 4.5 months with a 1-year rate at 19%. We concluded that paclitaxel is not active in terms of response as second-line chemotherapy for NSCLC.     

Second-line weekly paclitaxel in patients with inoperable non-small cell lung cancer who fail combination chemotherapy with cisplatin

This phase II study was designed to assess single-agent paclitaxel (Taxol), as second-line chemotherapy. Eligibility criteria: pathological diagnosis of inoperable non-small cell lung cancer (NSCLC) relapsing or refractory to standard front-line platinum (P)-based chemotherapy, performance status < or = 3, normal lab tests, informed consent. Ineligibility criteria: history of second or third cancer (unless surgically cured), mental instability or impairment, pre-existing moderate/severe peripheral neuropathy, previous chemotherapy non-including cisplatin, and previous second-line chemotherapy. Paclitaxel was given by intravenous infusion at a dose of 100 mg/m2 every week, until completion of the treatment plan of 21 weeks, disease progression, persistent toxicity, or patient refusal. Thirty-eight patients (32 males) entered the study; median age was 63 years (range 44-74); cell types were: adenocarcinoma (20), squamous (14), large cell (4). Previous chemotherapies: P and vinorelbine (31 patients) and P, mitomycin C and vinblastine (7 subjects), followed by 21 objective responses. Two patients had one course of paclitaxel; six other patients had early treatment suspensions. The median number of weekly infusions was 12 (range 1-21); median dose-intensity was 75% of projected. Toxicity was generally mild, mainly neurological and never life threatening (only 2 grade 4 toxicity out of 468 pre-chemotherapy evaluations). Six patients obtained a partial response; 7 others showed some tumor regression, 3 had tumor stabilization, and 13 disease progression. From the start of paclitaxel, the estimated median time to progression was 20 weeks, the median survival 58 weeks. Second-line treatment with single-agent paclitaxel is well-tolerated, active, and associated to long survivals.     

Phase I study of the combination of nedaplatin and weekly paclitaxel in patients with advanced non-small cell lung cancer

Purpose This trial was conducted to determine the maximum tolerated dose (MTD), principal toxicity, and recommended dose for phase II study of the combination of nedaplatin and weekly paclitaxel in patients with advanced non-small cell lung cancer (NSCLC). Methods Patients with previously untreated NSCLC, either stage IIIB with pleural effusion or stage IV, were eligible if they had a performance status of 0–2, were 75 years or younger, and had adequate organ function. The respective doses of nedaplatin (day 1) and weekly paclitaxel (days 1, 8, and 15) studied were 80/60, 80/70, 80/80, 80/90, and 100/90 (mg m⁻²), repeated every 4 weeks. Results From May 2004 through June 2005, 21 patients (18 men and 3 women; median age, 63 years; age range, 53–75 years) were enrolled. The MTD was determined to be 100 mg m⁻² of nedaplatin and 90 mg m⁻² of weekly paclitaxel. Dose-limiting toxicities at the MTD were neutropenic fever and hepatic dysfunction. We recommend doses of 80 mg m⁻² of nedaplatin and 90 mg m⁻² of weekly paclitaxel for phase II study. Grade 3–4 hematologic toxicities included neutropenia in 29% of patients, thrombocytopenia in 0%, and anemia in 5%. Although the most frequent non-hematologic toxicity was hepatic dysfunction, all cases were only mildly to moderately severe. Although two patients had grade 3 or 4 pulmonary toxicity due to Pneumocystis carinii pneumonia, these patients recovered after receiving trimetoprim-sulfamethoxazole, steroid therapy, and supplemental oxygen. There were no treatment-related deaths. The overall response rate was 19.0% (95% confidence interval, 5.4–41.9%), and all responses were in patients receiving the recommended doses. The median dose-intensities for nedaplatin and paclitaxel were 91.6 and 87.1%, respectively, of the planned doses. Conclusion This combination chemotherapy is active and well tolerated and warrants phase II study.     

Phase II study of weekly paclitaxel in patients with non-small cell lung cancer who have failed previous treatments

OBJECTIVE: New effective therapy is desirable for patients with non-small cell lung cancer (NSCLC) who have failed previous treatments. Fractionated administration of paclitaxel may be less toxic and more active against NSCLC. The aim of this study was to evaluate the activity and toxicity of weekly paclitaxel therapy for NSCLC in a second-line setting. METHODS: Patients with pathological or cytological diagnosis of NSCLC, measurable lesions, and one or more prior therapies were enrolled. We administered weekly infusions of 80 mg/m2 paclitaxel 3 times in a 4-week cycle. In the absence of progressive disease or intolerable toxicity, each patient was treated for a minimum of 4 cycles. RESULTS: Of 39 patients enrolled, 1 patient achieved complete response and 11 patients achieved partial response (response rate, 31%: 95% confidence interval, 17-48%). The median survival time was 43 weeks (range, 7-128 weeks). Grade 3 or 4 leukopenia occurred in only 7 patients (18%). Neurotoxicity was the most frequent adverse effect (grades 1 and 2.26 and 5%, respectively). Although all patients recovered rapidly with corticosteroid treatment, drug-induced pneumonitis was observed in 3 patients (8%). CONCLUSION: Low-dose weekly paclitaxel is a promising therapy with high effectiveness for advanced NSCLC in patients with NSCLC who have failed previous treatments.     

Second-line therapy with gefitinib in combination with docetaxel for advanced non-small cell lung cancer: a phase II randomized study

This randomized, open-label, parallel-group, phase II study evaluated the efficacy and safety of gefitinib and docetaxel in combination, as second-line therapy for advanced or metastatic non-small cell lung cancer (NSCLC). Eighty-nine patients who had failed first-line, platinum-based chemotherapy were randomly assigned to gefitinib (250 mg/day orally) in combination with docetaxel (75 mg/m² every 3 weeks) or single-agent docetaxel (75 mg/m² every 3 weeks). Objective response rates were 6.8% with gefitinib plus docetaxel and 9.1% with docetaxel alone. Disease control was experienced by a higher proportion of patients receiving gefitinib plus docetaxel (59.1%) versus docetaxel alone (34.1%). Median progression-free and overall survival appeared to be longer with gefitinib plus docetaxel (3.9 months [95% CI:2.3–5.4] and 7.6 months [95% CI:5.4–10.4], respectively) than with docetaxel alone (2.1 months [95% CI:2.1–3.7] and 6.2 months [95% CI:5.2–7.2], respectively). The most common non-hematological adverse events were diarrhea, alopecia, rash and dry skin in the combination arm, and vomiting and asthenia with docetaxel alone. Gefitinib and docetaxel combination therapy has antitumor activity and may be a feasible treatment option in patients with advanced NSCLC who have failed platinum-based chemotherapy.