Gemcitabine and vinorelbine followed by weekly docetaxel in patients with advanced non-small-cell lung cancer: a phase II trial of sequential chemotherapy

Objective We conducted this phase II trial to evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by weekly docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods Eligibility criteria: stage IV NSCLC, Performance status ≤2, adequate renal, hepatic and bone marrow function. Treatment consisted on: VNR 25 mg/m² plus gemcitabine 1000 mg/m², on days 1 and 8 of each 21-day cycle, followed by docetaxel 36 mg/m² weekly until progression or unacceptable toxicity. Results 21 stage IV patients were enrolled. All patients are evaluable for treatment response and toxicity profile. The mean age of the patients was 63 years (range: 51 to 72) with 18 (86%) males and 3 (14%) females. Histology types were: adenocarcinoma in 8 patients (38%), large cell carcinoma in 1 patients (5%) and squamous cell carcinoma in 12 patients (57%). The majority of the patients had and ECOG PS of 1. Eight patients (38%) did not complete six cycles of gemcitabine-navelbine. The median number of cycles of gemcitabine-navelbine was 4 (range 2–6). Of the 13 patients (61%) who completed six cycles of gemcitabine-navelbine, all of them went on to receive weekly docetaxel and received at least 3 cycles, with a median number of 8 cycles (range 3–16). The overall response rate was 33%. Respect survival, the minimum follow-up was 6 months (range, 6–25 months). The median survival time (MST) was 7.9 months, and the 1-year survival was 30%, and the median progression-free survival was 4.7 months. Toxicity was mild, well tolerated and mostly hematologic. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 14%, two patients with febrile neutropenia. Grade 3 anaemia in 1 patients (5%) and grade 3 thrombocytopenia in 1 patient (5%). Nonhematologic toxicity was also mild: 1 patient with Grade 3 skin toxicity with docetaxel, 1 patient with grade 3 infection, 2 patients with grade 3 astenia and 1 patient with a mild allergic reaction postchemotherapy treatment with docetaxel. Conclusion The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by weekly DOC is active and can be administered safely in advanced NSCLC. Our results are similar with other sequential regimens and did not represent a significant improvement in the treatment of this disease.     

Preoperative chemotherapy with cisplatin in combination with docetaxel and gemcitabine in locally advanced non-small-cell lung cancer

Despite surgery, both locoregional and distant disease controls remain poor in stage III non-small-cell lung cancer (NSCLC). Preoperative chemotherapy has become an accepted treatment but no established regimen exists. Our objective was to define the activity and feasibility of cisplatin in combination with docetaxel and gemcitabine in stage III NSCLC followed by surgery or radiotherapy. Thirty-two chemotherapy-naive patients with NSCLC (59% stage IIIAN2, 41% stage IIIB) received cisplatin 75 mg/m² on day 1, gemcitabine 1,000 mg/m² on days 1 and 8, and docetaxel 20 mg/m² on days 1, 8 and 15. Patients received induction chemotherapy (3 cycles) before re-evaluation, followed by thoracotomy or thoracic radiotherapy. Radiographic response was 50% and stable disease at computed tomography (CT) scan was observed in 30% of patients. Thirty patients were evaluable for response; thoracotomy was performed in 16 patients (53%) and resection was complete in 8 patients (27%). Grade 3/4 neutropenia, the main hematologic toxicity, occurred in 53% of patients but only 3 patients required hospitalization due to neutropenic fever. Severe non-hematologic toxicity was uncommon. There were 3 treatment-related deaths. To date, 22% of patients remain alive and disease-free with a median follow-up of 13 months. Median survival for all recruited patients was 14 months, with an estimated 1-year survival rate of 60%. The combination of cisplatin/docetaxel/gemcitabine is a welltolerated regimen. Although it has potential serious toxic effects, high response rates and manageable toxicity justify its use in further trials. The Spanish Lung Cancer Group (SLCG) is currently performing a trial with this regimen in stage III disease.     

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 II study of docetaxel and gemcitabine combination chemotherapy in non-small-cell lung cancer patients failing previous chemotherapy

We conducted a phase II study of docetaxel and gemcitabine chemotherapy in patients with non-small-cell lung cancer (NSCLC) who had not responded to previous chemotherapy, to assess the response to and toxicity of this combination chemotherapy. Thirty-six patients were enrolled from June 1999 to December 1999. Treatment consisted of docetaxel 30 mg/m(2) and gemcitabine 800 mg/m(2) intravenous infusion on days 1 and 8 every 3 weeks. One hundred forty-six cycles of treatment were given, with a median of four cycles (range, 1-8 cycles). All patients were evaluable for toxicity profile and response rate. The major toxicity was myelosuppression. Grade III or IV neutropenia occurred in 9 patients (25%) during treatment. Febrile neutropenia occurred in 2 patients (5.6%). Grade III or IV thrombocytopenia occurred in 6 patients (16.7%). Reversible fluid retention occurred in 9 patients (25%). Grade IV pulmonary toxicity (interstitial pneumonitis) occurred in two patients, and both died. Other toxicities were few and mild in severity. After two cycles of treatment, 13 patients (36.1%) had a partial response (95% CI 20.3-51.9%). There was no significant difference in the response rate among patients who had responded to previous chemotherapy or not. The median time to disease progression was 3.8 months, and the median survival was 6.9 months. Median survival was 7.1 and 4.9 months in patients receiving docetaxel and gemcitabine as second-line and greater than or equal to third-line chemotherapy, respectively. In conclusion, docetaxel and gemcitabine salvage chemotherapy produces a high response rate and a relatively mild toxicity profile in NSCLC. However, the issue of interstitial pneumonitis should be of concern.     

A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy

Purpose Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used as a first-line treatment of advanced gastric cancer (AGC). Docetaxel has shown promising activity against this disease. In this study, we explored the efficacy and safety of docetaxel monotherapy as salvage chemotherapy in AGC after F and P combination chemotherapy failed. Materials and methods From October 2004 to October 2005, 49 eligible patients were enrolled in this study. The median treatment-free interval was 28.0 days, and 81.6% of patients had suffered cancer progression within 4 months after the withdrawal of first-line chemotherapy. Docetaxel was given IV at a dose of 75 mg/m² every 3 weeks, together with dexamethasone prophylaxis. Results A total of 182 cycles of docetaxel were administered with a median of 3 (range 1–9) cycles. From an intention-to-treat analysis, eight patients achieved objective response with a response rate of 16.3% (95% CI, 6.0–26.6). The median response duration was 4.7 months. A total of 20 patients showed stable disease, but 17 patients suffered disease progression. At a median follow-up duration of 11.3 months for surviving patients (range 6.3–18.8 months), the median time to disease progression was 2.5 months (95% CI, 2.3–2.7) and the median overall survival time since the start of docetaxel monotherapy was 8.3 months (95% CI, 6.7–9.8). Grade 3/4 neutropenia and febrile neutropenia occurred in 18.4% of patients and in 5.4% of cycles. The incidence of non-hematologic toxicities of grade 3 or worse was asthenia 32.7%, diarrhea 10.2% and peripheral sensory neuropathy 8.2%. Conclusion Docetaxel at 75 mg/m² is active against AGC as second-line chemotherapy after prior exposure to F and P combination chemotherapy. The toxicity profile is moderate.     

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic gastric cancer

Purpose: Docetaxel, as a single agent, has demonstrated activity in patients with advanced gastric cancer and cisplatin has shown lack of overlapping toxicities with docetaxel. Therefore, we conducted a phase II study to assess the efficacy and the toxicity of a combination regimen of docetaxel plus cisplatin in patients with advanced gastric cancer who have never been treated with palliative chemotherapy. Methods: Ninety-two patients with metastatic gastric cancer were enrolled from April 2000 to March 2004. Patients with histologically confirmed gastric adenocarcinoma, at least one bi-dimensionally measurable lesion, no prior palliative chemotherapy and at least 6 months from the end of adjuvant chemotherapy were eligible for study entry. Docetaxel 75 mg/m² and cisplatin 75 mg/m² were given on day 1. The cycle was repeated every 3 weeks. The objective response was evaluated after three cycles of chemotherapy. Toxicity was assessed according to the National Cancer Institute common toxicity criteria scale version 2.0. Results: In total, 401 cycles were administered, with a median of 5 cycles per patient (range 1–9 cycles). The median age was 56 years (range 31–76). Eighty-six patients were evaluable for treatment response. The objective response rate was 43.5% (95% CI, 33.4–53.6) with one complete response and 39 partial responses. Twenty patients (21.7%) had stable disease and 26 patients (28.3%) had a progression. The median time to progression was 7.0 months (95% CI, 5.0–9.0) and the median overall survival was 11.5 months (95% CI, 9.5–13.4). The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia (17.4%), nausea/vomiting (13.0%) and diarrhea (7.6%). Conclusion: The combination chemotherapy of docetaxel with cisplatin in advanced gastric cancer was tolerable for most patients and showed a promising antitumor activity as a first-line therapy.Keon Woo Park and Jin Seok Ahn contributed equally to this work.     

Phase II trial of a 2-h infusion of gemcitabine plus carboplatin as first-line chemotherapy for advanced non-small-cell lung cancer

Purpose: To evaluate the efficacy and safety of the combination of using gemcitabine as a rate infusion of 10 mg/m² per min with carboplatin in front-line chemonaive patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Fifty-four chemonaive patients with stage IIIB or IV NSCLC have been included, 44 males and 10 females, with a median age 63 years (range 19–75). Thirty-two (59%) patients had adenocarcinoma, 13 (24%) squamous cell, 1 (2%) large cell carcinoma and 8 (15%) others. Eight (15%) had stage IIIB and 46 (85%) stage IV. Treatment was consisted of 1,200 mg/m² gemcitabine given as a 2-h continuous infusion (10 mg/m² per min) on days 1 and 8 of each cycle an AUC 5 carboplatin as on day 1, repeating each cycle for every 21 days. A total of 223 chemotherapy cycles were administered, with a median of four cycles per patient (range 1–6), and 15 (28%) patients received all six cycles. Results: Of the 54 patients enrolled, all were evaluated for toxicity and 51 assessed for response. The overall response rate was 41% (95% confidence interval, 28–57%) with complete and partial responses of 4 and 37%, respectively. The median time to disease progression was 5.0 months (95% CI, 3.7–6.3 months), and median overall survival time was 11.5 months (95% CI, 9.9–13.1 months). One-year survival was 42%. The main grade 3–4 toxicity (according to the WHO scale) consisted of neutropenia (56%) and thrombocytopenia (57%). Patients were required platelet transfusion in 27 cycles (12%) and hematopoietic growth factors support care in 56 (25%) cycles. No bleeding episodes were recorded. Grade 3 nausea/vomiting occurred in 6% and grade 1–2 skin rash occurred in 43%. Conclusions: Prolonged gemcitabine infusion combined with carboplatin is manageable and tolerated, and its efficacy is similar to that of other chemotherapeutic schemes used for NSCLC treatment.     

Gemcitabine plus vinorelbine for the treatment of advanced non-small cell lung cancer

The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy regimen of weekly gemcitabine and vinorelbine in patients with advanced non-small cell lung cancer (NSCLC). 40 chemotherapy-naı̈ve patients with stage IIIB/IV NSCLC were included. The doses of gemcitabine and vinorelbine were 1000 and 25 mg/m², respectively, given on days 1, 8 and 15, every 28 days. 38 patients were evaluable for response. One patient achieved a complete response (CR) and 10 attained a partial response (PR), for an overall response rate (ORR) of 29% (95% confidence interval (CI): 15–43%). 47% of patients experienced a clinical benefit. The main toxicity consisted of grade 3 anaemia and neutropenia in 5% of patients. Non-haematological toxicity was minimal. The dose-intensities were 744 mg/m²/week for gemcitabine and 15 mg/m²/week for vinorelbine. 40% of the patients survived for longer than 1 year. The median time to progression was 4 months and the median survival 8.5 months (95% CI: 3.1–13.8 months). The weekly administration of gemcitabine and vinorelbine is very well tolerated and results in an acceptable response rate for the treatment of NSCLC.     

Phase II trial of weekly docetaxel and gemcitabine as first-line therapy for patients with advanced non-small cell lung cancer

Background A platinum doublet has been the standard treatment for patients with advanced non-small cell lung cancer (NSCLC) and good performance status. This treatment results in almost a doubling of 1-yr survival, along with an improvement in quality of life despite treatment-related toxicities. However, platinum-based treatment may be associated with significant toxicity. Materials and Methods In this trial, we prospectively evaluated a weekly regimen of docetaxel and gemcitabine for advanced NSCLC. The endpoints of this study included objective response rate, survival, and toxicity. Forty-two patients with previously untreated, advanced NSCLC with PS 0-1 were included. Patients received docetaxel (36 mg/m²) and gemcitabine (600 mg/m²) on d 1, 8, and 15 of a 28-d cycle. Responses were assessed every two cycles. The median age was 63 yr; with 22 males and 20 females; 67% were ≥60 years old; and 38 patients had stage IV disease. Results In the intent-to-treat (ITT) analysis of response, 16 patients had a partial response (38%) and 15 patients had stable disease (36%). The 1-yr survival was 48%; median survival for all patients was 11.3 mo and the median progression-free survival was 5.1 mo. Toxicities (≥grade 3) included neutropenia (29%), asthenia (26%), diarrhea (14%), thrombocytopenia (10%), pneumonitis (7%), peripheral neuropathy (5%), peripheral edema (5%), nail changes (2%), and myositis (2%). Conclusions This study demonstrated that this non-platinum doublet (docetaxel+gemcitabine) given on a weekly schedule for advanced NSCLC was well tolerated with efficacy comparable to that reported with platinum-based chemotherapy regimens.     

A randomised phase II trial of two sequential schedules of docetaxel and cisplatin followed by gemcitabine in patients with advanced non-small-cell lung cancer

Purpose

The aim of this study was to determine the activity and toxicity of two sequential chemotherapy regimens in the first-line treatment of advanced non-small-cell lung cancer (NSCLC).

Methods

Eighty-eight chemonaive patients with stage IIIB/IV NSCLC were randomised to receive either three cycles of 75?mg/m² cisplatin plus 75?mg/m² docetaxel, both administered on day 1 every 21?days, followed by three cycles of 1,200?mg/m² gemcitabine on days 1 and 8 every 3?weeks (arm A), or three cycles of 25?mg/m² cisplatin plus 25?mg/m² docetaxel on days 1, 8 and 15 every 28?days, followed by three cycles of 1,200?mg/m² gemcitabine on days 1 and 8 every 3?weeks (arm B).

Results

Of the evaluable patients, 61% in arm A (n?=?41) and 36% (n?=?44) in arm B completed treatment as per the protocol. The best tumour response rates were as follows (arm A and arm B): complete response: 2.4 and 2.3%; partial response: 39 and 20.4%; stable disease: 26.8 and 13.6%; and progressive disease: 31.8 and 45.4%. The median progression-free and overall survival were 3.9 and 12.3?months in arm A, respectively, 3.1 and 7.7?months in arm B. Grade 3?C4 adverse events were more common in arm A. Grade 3?C4 neutropenia was the main toxicity observed (56.1% in arm A and 11.4% in arm B).

Conclusions

Our data demonstrate the feasibility of a sequential approach of cisplatin plus docetaxel followed by single-agent gemcitabine. Weekly administration of platinum-docetaxel is associated with an improved safety profile but lower efficacy than the conventional three-weekly schedule (registration ID 2004-001044-72).     

Cisplatin plus continuous infusion vinorelbine for the treatment of advanced non-small cell lung cancer: a phase I-II study

Backbround In this Phase I/II trial, the maximum-tolerated dose (MTD) and activity of cisplatin plus vinorelbine (VRL) administered in continuous in-fusion as first-line treatment of advanced non small cell lung cancer (NSCLC) was determined in 12 consecutive chemotherapy-naive patients with advanced NSCLC. Patients and methods The dose of cisplatin was 100 mg/m² in all patients, and vinorelbine was administered as an initial intravenous (iv) bolus of 8 mg/m² on day 1 followed by a 4-day continuous iv infusion at 4 different 24 h dose levels (DLs) to be repeated every 21 days. All 12 patients (47 cycles) were evaluable for response and toxicity. Results The MTD was 8 mg/m² bolus followed by a continuous iv infusion of 8 mg/m² per day over 4 days. The dose limiting toxicities (DLT) were febrile neutropenia in 4 patients and grade 3 mucositis in 1 patient. There was less neuro-toxicity and compared to the weekly bolus scheme. There was no significant cumulative toxicity after 3 cycles. Partial responses were observed in 6 patients; an overall response rate of 50% (95% CI: 30–65%). Median time to progression was 5,5 months (95% CI: 1,5–11 months) and median survival was 11 months (95% CI: 5–20 months). Conclusions The results demonstrate that, in this setting of first-line treatment of NSCLC, cisplatin plus vinorelbine at 8 mg/m² bolus followed by a continuous infusion of 8 mg/m² per day over 4 days is the recommended schedule. Further trials would be useful to establish activity of this combination.     

Sequential doxorubicin and docetaxel as first-line treatment in metastatic breast cancer: a GEICAM-9801 phase II study

Purpose. To evaluate the efficacy and the toxicity profile of the sequential administration of doxorubicin and docetaxel as first-line chemotherapy in metastatic breast cancer (MBC). Patients and methods. Eighty-one patients received a total of 436 cycles of chemotherapy: 236 of doxorubicin (75 mg/m²) and 200 of docetaxel (100 mg/m² every 21 days). The first 35 patients received doxorubicin every 14 days with G-CSF support, and in the other 46 cases doxorubicin was administered every 21 days without G-CSF. Results. After entire treatment the overall response rate was 65% (18 complete responses). With a median follow-up of 19 months (range, 1–48 months), the median time to progression was 11.3 months and the median survival time was 31 months. As expected, febrile neutropenia was the most important toxicity and it appeared in 26 cycles (6%) and 19 patients (23%). In the patients that received doxorubicin every 14 days, the febrile neutropenia incidence was higher during docetaxel treatment, especially after its first administration. Conclusions. The dose and schedule of doxorubicin and docetaxel used in this trial seems to be active in first-line treatment of patients with MBC. The toxicity profile appears to be better than observed with concomitant schedules.     

A phase I/II trial of docetaxel and oxaliplatin in patients with advanced gastric cancer

Purpose  We designed this phase I/II study of docetaxel–oxaliplatin combination chemotherapy to determine the dose-limiting toxicity (DLT), maximum tolerated dose and efficacy as a first-line treatment in patients with advanced gastric cancer. Methods  Patients with histologically proven, chemo-naive gastric adenocarcinoma were eligible. For the phase I part, three dose levels of oxaliplatin and docetaxel every 3 weeks were tested in a cohort of three patients for each level (respectively, 100 and 60 mg/m², 100 and 75 mg/m², 130 and 75 mg/m²). Patients were treated up to a maximum of nine cycles of oxaliplatin and docetaxel unless there was documented disease progression, an unacceptable adverse event, or withdrawal of consent. Results  No DLT was observed at any of the three levels tested in the phase I portion. Therefore, oxaliplatin 130 mg/m² and docetaxel 75 mg/m² were recommended for the phase II study. All 47 patients were evaluable for toxicity and treatment response. The overall response rate was 55.3% (95% CI, 40.6–70.1%) and median duration of response was 4.2 months (range 0.9–9.5 months). After a median follow-up duration of 13.3 months, median overall survival was 12.7 months (95% CI: 10.4–14.9). The median time to progression was 5.0 months (95% CI, 3.4–6.5 months). The main toxicities (grade 3 or 4) were febrile neutropenia (14.9%), neutropenia (23.4%), diarrhea (10.6%) and neurotoxicity (8.5%). Conclusion  The combination of docetaxel and oxaliplatin was feasible with favorable toxicity profile and showed a promising anti-tumor activity in unresectable, metastatic gastric cancer patients.     

The efficiency of single agent docetaxel in patients with platinum-refractory non-small cell lung carcinoma

Summary   Background To evaluate the efficiency of docetaxel as second line chemotherapy in patients with platinum-refractory non-small cell lung carcinoma (NSCLC). Patients and methods Fifty-two patients with locally advanced or metastatic NSCLC who had platinum-refractory disease (progressed through or within 3 months of completion of first line therapy) and an Eastern Cooperative Oncology Group performance (ECOG) status 0–2 were treated with second-line chemotherapy consisting of single agent docetaxel (100 mg/m², intravenously, on day 1 of a 21-day cycle). The median number of treatment cycles was 4 (2–6). Disease-free (DFS) and overall survival (OS), response rates and toxicity were evaluated. Results The median progression-free survival of patients was 3 months (95% CI: 0.01–5.99) and overall survival was 7.2 months (95% CI: 2.2–9.5). One-year overall survival rate was 29%. Disease control (complete response, partial response, or stable disease) was achieved in 25 patients (48%) and overall response rate was 13% (7 patients). There were no complete responses. Seventeen patients (33%) had stable disease and twenty-seven patients (52%) had progressive disease. Age, gender, stage at diagnosis (IIIB vs. IV), performance status at initiation of second-line therapy (0–1 vs. 2) histopathological type (epidermoid vs. others), grade, LDH, albumin, weight loss were evaluated as prognostic factors; however, none of these had a significant affect on survivals. The protocol was well tolerated and there were no toxic deaths. Grade III–IV anemia was present in 8 patients (15%) and thrombopenia in 12 (23%) patients. The most frequent grade 3–4 toxicities were leucopenia (52%) and neutropenia (48%). Febril neutropenia occurred in 14 patients (26%). No patients experienced grade III–IV mucositis and diarrhea. Totally, the need of a dose reduction was about 25% and treatment delay (4–9 days) occurred in 5 patients (10%) and 7 patients (13%), respectively, because of toxicity. Conclusions Second-line chemotherapy with single-agent docetaxel offers a small but significant survival advantage with acceptable toxicity for patients with advanced NSCLC who have platinum-refractory disease.     

Phase II study with fractionated schedule of docetaxel and cisplatin in patients with advanced non-small cell lung cancer

Background

Docetaxel and cisplatin combination chemotherapy is established first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). We evaluated a weekly schedule of docetaxel and cisplatin for efficacy and tolerability in patients with chemotherapy-naive NSCLC.

Methods

Patients enrolled in this study had stage IIIB or IV NSCLC with measurable disease, no prior chemotherapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. Treatment consisted of docetaxel 40 mg/m² and cisplatin 35 mg/m² given on D1 and D8 every 3 weeks. Patients were evaluated for response after every 2 cycles of treatment.

Results

Thirty six patients were enrolled, and 35 underwent treatment. Of these, 29 were males and 7 females, median age was 61 years (range, 38–68). About 31 patients had ECOG PS 0-1 and 4 patients had ECOG PS 2. Fifty seven percentage (20/35) of patients had adenocarcinoma and 74.3% (26/35) had stage IV disease. A total of 153 cycles of chemotherapy were administered. Of the 35 patients treated, 17 (48.6%) achieved partial response, 11 (31.4%) showed stable disease, and 6 (17.1%) had progressive disease. Median duration of response was 5.3 months (95% CI: 4.2–6.2 months), and median time to disease progression was 4.6 months (95% CI: 2.9–6.3 months). Estimated overall survival at 1 year was 65.7%. The major hematologic toxicity was myelosuppression. Grade 3 or 4 anemia occurred in 6 cycles, and grade 3 or 4 neutropenia was observed in four cycles. Major non-hematologic toxicities were grade 3 nausea in three patients and grade 3 fatigue in two patients. Three patients developed pneumonia and one patient had infectious colitis. There were no treatment-related deaths in this study.

Conclusions

Weekly schedule of docetaxel and cisplatin as first-line treatment for NSCLC had good efficacy and manageable toxicity.     

Fixed-dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor performance status patients with unresectable non-small cell lung cancer

Purpose  We investigated the efficacy and toxicity of a 4-week schedule of a fixed dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor performance status patients with unresectable non-small cell lung cancer (NSCLC). Methods  In this study, 48 patients with previously untreated NSCLC were given combination chemotherapy that consisted of gemcitabine 1,000 mg/m² (10 mg/m²/min fixed dose rate infusion) and cisplatin 25 mg/m², and both drugs were given weekly on days 1, 8 and 15. Results  A partial response and stable disease were observed in 20 patients (41.7%, 95% CI; 27.8–55.6%) and 12 patients (25.0%), respectively. The overall median survival was 10.30 months (range: 7.85–12.74 months). Major toxicities included neutropenia (grade 3 to 4, 29.2%) and infection (grade 3 to 4, 27.1%). Conclusions  Our results indicate that this regimen is a feasible treatment for elderly or poor performance status patients with unresectable NSCLC. Nevertheless, the morbidity due to myelosuppression and infection following this treatment should be carefully considered. G.-W. Lee and M.-H. Kang contributed equally to this work.     

A phase II study of irinotecan and docetaxel combination chemotherapy for patients with previously treated metastatic or recurrent advanced gastric cancer

Purpose  Irinotecan (I) and docetaxel (D), each of which has a unique mechanism of action, were recently introduced in the treatment of patients with advanced gastric cancer (AGC). We have evaluated the efficacy and safety of the ID combination for AGC patients after failure of fluoropyrimidine- or platinum-based chemotherapy. Materials and methods  Patients with relapsed or progressive AGC after prior fluoropyrimidine- or platinum-based chemotherapy were treated with I (160 mg/m², 90 min) followed by D (65 mg/m², 1 h) every 3 weeks. Because of the unacceptable toxicity among the first ten patients, the doses were reduced for I (120 mg/m²) and D (50 mg/m²) every 3 weeks. Results  Forty-nine patients, of median age 53 years (range, 27–68 years), were treated with 170 cycles of chemotherapy (median, 2 cycles; range, 1–12 cycles). Three patients achieved complete response and seven achieved partial response, resulting in an overall response rate (ORR) of 20.4% [95% confidence interval (CI), 9.1–31.7%], with a median duration of 7.1 months (range: 2.1–69.1 months). ORR was 60% (95% CI, 29.6–90.3%) for the higher dose and 10.3% (95% CI, 0.7–19.8%) for the lower dose. Median time to progression for all patients was 2.7 months (95% CI, 1.7–3.8 months) and the median overall survival was 8.9 months (95% CI, 6.6–11.3 months). Grade 3/4 toxicities included neutropenia (90%), febrile neutropenia (50%), asthenia (40%), and diarrhea (10%) with the higher dose and neutropenia (71%), febrile neutropenia (11%), diarrhea (24%), and asthenia (24%) with the lower dose. There were two possible treatment-related deaths. Conclusion  The combination of irinotecan and docetaxel, once every three weeks shows anti-tumor activity but is not feasible as a second-line treatment for AGC patients after failure of fluoropyrimidine- or platinum-based chemotherapy due to the high rate of toxicities. S. J. Sym and H. M. Chang have contributed equally to this article.     

Combination of topotecan and etoposide as a salvage treatment for patients with recurrent small cell lung cancer following irinotecan and platinum first-line chemotherapy

Purpose The efficacy and safety of a combined regimen of topotecan and etoposide was tested in patients with relapsed or refractory small-cell lung cancer. Patients and methods From October 2003 to May 2005, 23 patients who have failed to the previous irinotecan and platinum chemotherapy received intravenous topotecan 1 mg/m² (day 1–5) and etoposide 80 mg/m² (day 1–3). Treatment was repeated every 21 days for a maximum of 6 cycles. Results Twelve patients were refractory to first-line chemotherapy. Seventeen patients (73.9%) were male and the median age was 63 years. ECOG performance status was 0–1 in 13 (56.5%) patients. The median cycles of chemotherapy was three. Twenty-one patients were assessable for response evaluation. The overall response rate was 17.4% (0 CR, 4 PR, 7 SD, 10 PD) under the intent-to-treat analysis. Two sensitive case patients and two refractory case patients achieved partial response. After a median follow-up of 20.8 months, median progression free survival was 4.7 months and median overall survival was 9.5 months. The estimated 1-year survival rate was 38.7%. All patients were assessable for toxicity and major toxicities were myelosuppression. Grade 3/4 neutropenia and thrombocytopenia occurred in 18 (78.3%) and 12 (52.2%) patients, respectively. Grade 3/4 febrile neutropenia occurred in two patients (8.7%) and infection in three patients (13.0%). There was one treatment-related death due to pneumonia. Conclusion This salvage regimen showed modest efficacy and manageable toxicities. Further study will be required in recurrent SCLC patients pretreated irinotecan and platinum.     

Docetaxel and mitomycin as second-line treatment in advanced non-small cell lung cancer

Purpose: To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m²) followed by mitomycin C (8 mg/m²) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected. Results: A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3–4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6–21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%. Conclusions: The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate.     

Gemcitabine and paclitaxel chemotherapy for advanced urothelial carcinoma in patients who have received prior cisplatin-based chemotherapy

Background  The objective of this study was to evaluate the efficacy and toxicity of combination chemotherapy with gemcitabine and paclitaxel as a second-line regimen in patients with advanced urothelial carcinoma. Methods  Twenty patients with advanced urothelial carcinoma who were resistant to an M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy regimen were administered chemotherapy consisting of intravenous gemcitabine 2500 mg/m² and paclitaxel 150 mg/m² (GP) every 2 or 3 weeks. Results  The patients received a median of 7.7 cycles of treatment (range, 2–20 cycles). Six of the 20 patients (30%; 95% confidence interval [CI], 10%–50%) had a major response to treatment (a complete response [CR] in 5% and a partial response [PR] in 25%). Seven patients (35%) had stable disease (SD). The median duration of response was 4.5 months (range, 1–9 months) and the disease control rate (CR + PR + SD) was 65%. The median survival was 11.5 months (range, 2–22 months) and the 1-year survival rate was 35%. The patients tolerated this regimen well, with only grade 3–4 neutropenia being observed in 6 patients (30%), anemia in 3 (15%), and thrombocytopenia in 1 (5%). The response rate to M-VAC in the first-line chemotherapy was significantly associated with the response to GP as the second-line chemotherapy. Conclusion  The combination of gemcitabine and paclitaxel is active and well tolerated as a second-line treatment in patients with advanced urothelial carcinoma.