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.     

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.     

Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study

Background Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy. Methods This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m² (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m² (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC. Results Forty-one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182 chemotherapy cycles (median 6, range 1–6) was administered to 40 patients during the study; one patient did not receive chemotherapy due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44% (95% CI, 29–59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except for pulmonary toxicity. The main grade 3–4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases of febrile neutropenia were reported. The main grade 3–4 non-hematological toxicity was pulmonary toxicity (23% of patients, 6% of cycles). Conclusion Gemcitabine 1,000 mg/m² on days 1 and 8 in combination with docetaxel 85 mg/m² on day 8 given in 3-week cycles is an active and well-tolerated first-line chemotherapeutic regimen for advanced NSCLC.     

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.     

Docetaxel monotherapy as a second-line treatment after failure of fluoropyrimidine and platinum in advanced gastric cancer: experience of 154 patients with prognostic factor analysis

OBJECTIVE: To investigate the efficacy and safety of docetaxel monotherapy as salvage chemotherapy for advanced gastric cancer (AGC) in clinical practice and to determine the prognostic factors in these patients. METHODS: We retrospectively reviewed the medical records of patients with AGC for whom fluoropyrimidine and platinum had previously failed and who had received docetaxel salvage monotherapy between December 2000 and March 2006. Docetaxel was administered at a dose of 75 mg/m(2) intravenously every 3 weeks with dexamethasone prophylaxis. RESULTS: A total of 154 patients received 583 cycles of docetaxel with a median of three cycles per patient (range 1-10). The median age was 54 years (range 27-75 years). The objective response rate of 86 patients with measurable lesions was 14%, with 1 complete response and 11 partial responses, with a median response duration of 5.6 months. An additional 25 patients achieved stable disease. The median time to progression (TTP) for all patients was 2.6 months [95% confidence interval (CI), 2.2-2.9] and the median overall survival (OS) from the start of docetaxel chemotherapy was 7.2 months (95% CI, 5.9-8.5). The chemotherapy was generally well tolerated. Multivariate analysis showed that the Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 versus 2) was an independent prognostic factor for both TTP and OS. Disease status indicative of a relatively small tumor burden (resected metastatic or recurrent tumor) was a predictor for better TTP and good differentiation of the tumor was a predictor for better OS. CONCLUSION: Docetaxel 75 mg/m(2) is relatively active and tolerable as a second-line salvage treatment after failure of fluoropyrimidine and platinum in general clinical practice for AGC.     

A multicentre phase II study to evaluate sequential docetaxel followed by capecitabine treatment in anthracycline-pretreated HER-2-negative patients with metastatic breast cancer

Introduction  Treatment of HER-2-negative metastatic breast cancer (MBC) patients after anthracycline exposure is controversial. Docetaxel/capecitabine is a promising regimen, but the administration schedule is not well established. Materials and methods  Treatment included 3 cycles of docetaxel 100 mg/m² day 1 every 21 days followed by 3 cycles of capecitabine 1250 mg/m²/12 h days 1–14. Patients not progressing were maintained with capecitabine 900 mg/m²/12 h on days 1–14 every 21 days until progression or unacceptable toxicity. Results  Fifty-three anthracycline-pretreated patients were enrolled: median age 54 years, ECOG grade 0–1 86.7%. Most of the women received adjuvant chemotherapy (81%) and 5 patients (9%) had had prior metastatic chemotherapy treatment. Median time from anthracycline exposure was 29 months. ORR (intent-to-treatment analysis) after the sequential therapy was 51% (CI 95% 37–65) with 15% (CI 95% 7–28) of patients reaching complete responses. Median time to progression was 8.2 (CI 95% 7.1–10.7) months, with 61.9% (CI 95% 45.6–76.4) of the patients free of disease after 6 months. Median overall survival was not reached after a median follow-up of 10.4 months, and 75% of the patients were alive after 14.3 months. Survival rate after 12 months was 81.1% (CI 95% 68.0–90.6). The most frequent NCI grade 3–4 toxicities were hair loss (28.3%), asthenia (15.1%), stomatitis (11.32%) and nausea (11.32%). Severe hand-foot syndrome rate was 7.5%. Conclusions  Sequential docetaxel-capecitabine is feasible, effective and well tolerated in first-line MBC treatment. Evaluation of this schedule in randomised studies is warranted.     

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.     

Sequential vinorelbine–capecitabine followed by docetaxel in advanced breast cancer: long-term results of a pilot phase II trial

Purpose To evaluate the response rate of the combination of capecitabine (C) and vinorelbine (V) followed by Docetaxel (D) in the 1st line treatment of advanced and metastatic breast cancer patients. Patients and methods Patients with measurable disease and no prior chemotherapy in advanced disease were eligible. Pts received V 25 mg/m² on day 1 and 8 in combination with C 825 mg/m² twice a day from day 1 to 14 every 3 weeks for four cycles followed by 12 consecutive weeks of D 25 mg/m²/w. Results Between March 2002 and November 2003, 40 patients were enrolled. Median age was 57 years. Of patients, 77.5% of pts had visceral involvement and 32.5% had more than two metastatic sites. In the adjuvant setting, 62.5% received anthracycline and 10% Taxanes. In the intent-to-treat population, an overall objective response was observed in 25 patients (62.5, 95% CI, 45.8–77.27) and stable disease in 5 (12.5%). Median time till progression (TTP) was 12.3 months (range 1.5–48; 95% CI, 10.05–14.54). The median survival was 35.7 months (range 2–47). Reported grade 3–4 toxicities under Navcap were neutropenia (4 pts), anemia (1 pt), thrombopenia (1 pt) and febrile neutropenia (3 pts). Reported grade 3–4 toxicities under weekly Docetaxel were neutropenia (1 pt), thrombopenia (2 pts), leucopenia (1 pt) and anemia (1 pt). Conclusion The sequential use of Navcap followed by weekly Docetaxel demonstrated an interesting efficacy with a prolonged TTP and OS and warrants further evaluation. This study was supported in part by Institut de Recherche Pierre-Fabre and by sanofi-aventis.     

Phase II multicenter trial of docetaxel, epirubicin, and 5-fluorouracil (DEF) in the treatment of advanced gastric cancer: a novel, safe, and active regimen

Background This study evaluated the efficacy and safety of docetaxel, epirubicin, and 5-fluorouracil (5-FU) [DEF] as treatment for locally advanced unresectable or metastatic gastric cancer. Methods Thirty-seven patients participated in the study (median age, 56 years; range, 22–73 years); Eastern Cooperative Oncology Group performance status [PS], 0–2). Docetaxel 75 mg/m² IV (day 1), 5-FU 500 mg/m² IV (days 1–3), and epirubicin 50 mg/m² IV (day 1) were administered every 3 weeks for six cycles. Results In total, 20/37 patients (54%) completed six treatment cycles. Thirteen patients (35%; 95% confidence intervals [CI], 20% to 51%) had an objective response; 1 patient (3%) achieved a complete response and 12 patients (32%) achieved partial responses. Stable disease was observed in 7 patients (19%) and progressive disease in 5 patients (14%). Twelve patients (32%) were unevaluable. Clinical benefit (based on PS, weight gain, and analgesic consumption) was observed in 11 patients (30%). Median follow-up was 41 months (range, 26–53 months), median time to progression was 6.6 months (range, 0.5–29.2 months), median overall survival was 10.7 months (range, 7.0–14.6 months), and 1-year survival was 40%. The regimen was well tolerated. Grade 3–4 febrile neutropenia occurred in 8 patients (22%; 6% of cycles) and grade 3–4 neutropenia in 1 patient (1% of cycles). The most frequent grade 3–4 toxicities were alopecia (11% of cycles), diarrhea (4% of cycles) and vomiting (2% of cycles); grade 1–2 asthenia and fatigue occurred in 43% of cycles. Conclusion DEF is effective in the treatment of advanced gastric cancer, and has a good safety profile. Presented at: 2002 ASCO Meeting (Poster Section): Proc Am Soc Clin Oncol 2002;21:163a and 2002 ESMO Meeting (Poster Section): Ann Oncol 2002;13(Suppl 5):192     

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.     

Capecitabine in combination with Oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer

Purpose We evaluated efficacy and safety of XELOX in previously untreated patients with AGC. Patients and methods Patients received intravenous oxaliplatin 130 mg/m² over 2 h on day 1 plus oral capecitabine 1,000 mg/m² twice daily on days 1–14, every 3 weeks (XELOX). Treatment was continued until disease progression, intolerable toxicities or eight cycles reached. All tumour evaluations were reviewed and confirmed centrally. Design was according to Ensign’s three-stage method. Results Fifty-four patients (37 men) were enrolled; median age 57 years (range 29–70). In total, 311 cycles of XELOX were delivered. Overall response rate was 63% (95% CI, 50–76%), with 3 complete and 31 partial responses. At 13 months’ median follow-up, median progression-free and overall survival were 5.8 (95% CI, 4.4–7.2) and 11.9 months (95% CI, 8.8–15.1), respectively. The most common haematological adverse event was anaemia (70% of patients). Grade 3–4 neutropenia was observed in four patients, with neutropenic fever in only one patient. Most common non-haematological toxicities were neuropathy (70%), vomiting (50%), diarrhoea (33%), and hand-foot syndrome (HFS) (39%). Grade 3–4 toxicities were rare. Treatment was delayed or the dose reduced in 30 and 15% of cycles, respectively. There was one treatment-related death associated with grade 4 neutropenic sepsis. Conclusion XELOX was active and well tolerated as a first-line therapy for AGC.     

Docetaxel, 5-fluorouracil, and leucovorin as treatment for advanced gastric cancer: results of a phase II study

Background: Previous studies have shown that the taxane, docetaxel, is effective in treating gastric cancer. The aim of this study was to assess the efficacy and safety of docetaxel in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Methods: Thirty patients with histologically proven locally advanced and/or metastatic gastric cancer with WHO performance status 0–2 were enrolled and received either 75 or 100 mg/m² docetaxel as a 1-h intravenous infusion on day 1 every 28 days. All patients also received 5-FU (1800 mg/m²) plus LV (500 mg/m²), by continuous intravenous infusion over 24 h on days 1, 8, and 15 every 28 days. Chemotherapy was given for at least two cycles. Results: Of the 25 evaluable patients, 3 showed a complete response, 4 showed a partial response, and 11 patients had stable disease. The overall response rate was 28.0% (95% confidence interval [CI], 10.4, 45.6). The median time to progression was 5.9 months (95% CI, 5.4, 6.5), and the median overall survival was 7.7 months (95% CI, 7.2, 8.3) for the intent-to-treat population. The most frequent grade III and IV hematological toxicities were neutropenia and anemia. Febrile neutropenia was observed in 10% of patients and 2.4% of cycles. The prophylactic use of granulocyte colony-stimulating factor (G-CSF) in 3 patients reduced the incidence and severity of neutropenia. Other hematological toxicities were rare. Conclusion: Docetaxel in combination with weekly 5-FU and LV is effective in treating patients with advanced/metastatic gastric cancer. This new docetaxel-containing combination shows promise as a third-generation treatment option for gastric cancer. Received: December 25, 2001 / Accepted: April 22, 2002 Offprint requests to: M. Constenla     

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.     

A phase II study of weekly docetaxel in patients with anthracycline pretreated metastatic breast cancer

Background: Docetaxel has significant activity in metastatic breast cancer and weekly schedules are associated with less myelosuppression than 3-weekly schedules. We evaluated the toxicity and the activity of weekly docetaxel in anthracycline-pretreated patients. Patients and methods: A total of 42 patients were studied. Treatment consisted of docetaxel 35 mg/m² weekly as a 30-min infusion for 6 weeks followed by a 2-week rest, with dexamethasone 8 mg i.v. pre-medication and 4 mg orally 12-hourly for 48 h following treatment. Results: The median age of the patients was 53 years (range 34–74). Twenty-six (62%) patients had received prior chemotherapy for advanced disease. Patients received a median 10 weeks of treatment (range 1–24). 11 had a partial response (ORR 26%; 95% CI 13–39%), five of whom had relapsed <12 months since the end of previous anthracycline-based chemotherapy. In addition six patients (14%) had stable disease for >16 weeks. Myelosuppression was rare with only 2 patients (5%) experiencing grade 3 neutropenia (no grade 4 neutropenia). Non-haematological grade III toxicities were as follows: fatigue 17%, neuropathy 0%, hyperlacrimation 5%, stomatitis 7%, diarrhoea 14%, and cutaneous toxicity 19%. Skin toxicity consisted of limb/palmar–plantar erythematous reactions, or fixed-plaque erythrodysaesthesia. Conclusions: Weekly docetaxel has moderate activity in women with anthracycline pre-treated breast cancer. Although the level of myelosuppression is lower than 3-weekly regimens, this weekly regimen cannot be recommended due to the significant non-haematological toxicities associated with the treatment.     

Capecitabine and doxorubicin combination chemotherapy as salvage therapy in pretreated advanced gastric cancer

Purpose The aim of this study was to evaluate the activity and the safety of a combination regimen of capecitabine and doxorubicin as salvage chemotherapy in advanced gastric cancer patients who had undergone one or two prior chemotherapy regimens. Methods Patients received capecitabine, 2,500 mg/m²/day PO for 14 days (D1–14) and doxorubicin, 30 mg/m² IV on day 1 every 3 weeks until disease progression. The response was evaluated according to RECIST criteria, and the toxicity was evaluated by NCI-CTC (version 2.0). Results Forty-five patients were enrolled. Twenty-six patients were treated as second-line chemotherapy and the remaining patients as third-line chemotherapy. A total of 152 cycles of chemotherapy (median 2, range 1–12) were administered. Median dose intensities of capecitabine and doxorubicin were 11,326 and 9.6 mg/m²/week, respectively. The overall response rate was 6.7% (95% CI, 4.1–12.5%) and the disease control rate was 46.7% (95% CI, 28.6–87.1%) according to an intent-to-treat analysis. The median progression-free survival was 11.3 weeks (95% CI, 5.6–16.7 weeks). The median overall survival was 29.1 weeks (95% CI, 18.3–39.9 weeks) with one-year survival rate of 24%. Severe (grade III/IV) hematologic and non-hematologic toxicity was uncommon and included nausea/vomiting in five (11.1%), neutropenia in two (4.4%), anemia in one (2.2%), and hand-foot syndrome in one patient (2.2%). Conclusions The combination of capecitabine and doxorubicin is a feasible salvage regimen in advanced pre-treated gastric cancer.     

Additive effects of a prolactin receptor antagonist,G129R,and herceptin on inhibition of HER2-overexpressing breast cancer cells

Genexol-PM is a novel Cremophor EL-free polymeric micelle formulation of paclitaxel. This single arm, multicenter phase II study was designed to evaluate the efficacy and safety of Genexol-PM in patients with histologically confirmed metastatic breast cancer (MBC). Forty-one women received Genexol-PM by intravenous infusion at 300 mg/m² over 3 h every 3 weeks without premedication until disease progression or intolerability. A total of 331 chemotherapy cycles were administered, with a median of 8 cycles per patient (range, 1–16). Overall response rate was 58.5% (95% CI: 43.5–72.3) with 5 complete responses and 19 partial responses. Thirty-seven patients who received Genexol-PM as a first-line therapy for their metastatic disease showed a response rate of 59.5% (95% CI: 43.5–73.7), and two responses were reported in four patients treated in the second-line setting for their metastatic disease. The median time to progression (TTP) for all patients was 9.0 months (range, 1.0–17.0+ months). Grade 3 non-hematologic toxicities included sensory peripheral neuropathy (51.2%), and myalgia (2.4%). Eight patients (19.5%) experienced hypersensitivity reactions, with grade 3 in two patients. Hematologic toxicities were grade 3 and 4 neutropenia (51.2 and 17.1%, respectively), and grade 1 and 2 thrombocytopenia (22.0%). Notably, no febrile neutropenia was observed. Genexol-PM appears a promising new paclitaxel in view of significant efficacies. Further trials with different dosing schedules, durations of delivery, or in combination with other drugs are warranted.     

Docetaxel and granulocyte colony-stimulating factor in patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapy: a multicenter phase II trial

Purpose: To investigate the activity of docetaxel and granulocyte colony-stimulating factor support (G-CSF) in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with cisplatin. Patients and methods: A total of 60 patients with locoregional and metastatic NSCLC who had relapsed or progressed after first-line treatment with cisplatin-based regimens were enrolled into the trial. Docetaxel at 100 mg/m² was given as a 1-h infusion with G-CSF (rhG-CSF given s.c. at 150 μg/m²) support from day 2 to day 8 every 3 weeks; all patients received premedication with corticosteroids. Results: In all, 1 (1.6%) and 14 (23.3%) patients achieved a complete response (CR) and a partial response (PR), respectively, for an overall response rate of 25% (95% CI 14.0–35.9%); stable disease (SD) and progressive disease (PD) were documented in 18 (30%) and 27 (45%) patients, respectively. The median duration of response was 20 weeks and the median time to tumor progression was 28 weeks. The median overall survival was 32 weeks and the 1-year survival rate was 23%. A total of 263 courses were given at a median of 3 cycles/patient. Grade 3 and 4 neutropenia occurred in 11 (18%) and 14 (23%) patients, respectively, with 18 (30%) patients requiring hospitalization for neutropenic fever; 1 patient died of sepsis. Grade 2 peripheral neuropathy occurred in 9 patients (15%) and grade 3 asthenia, in 4 (7%). Other toxicities were mild. Conclusions: Docetaxel has considerable single-agent activity in patients with NSCLC who have relapsed or progressed after first-line chemotherapy with cisplatin-based regimens. Received: 17 June 1998 / Accepted: 17 August 1998     

Docetaxel plus epirubicin is a highly active, well-tolerated, first-line chemotherapy for metastatic breast cancer: results of a large, multicentre phase II study

Purpose In this multicentre phase II study, the efficacy and safety profile of the combination of docetaxel and epirubicin as first-line chemotherapy for metastatic breast cancer (MBC) were evaluated.Methods Epirubicin (75 mg/m²) and docetaxel (75 mg/m²) were given intravenously once every 3 weeks for six cycles to 133 patients with MBC.Results The overall clinical response rate was 67% (complete and partial responses were 23% and 44%, respectively). The median time to progression was 10.8 months (95% CI 9.7–12.6) and the median overall survival was 19.5 months. Granulocyte colony-stimulating factor support was administered to 32% of patients and in 22% of cycles. Grade 3/4 neutropenia occurred in 35% of patients and febrile neutropenia in 19%. The most frequent grade 3/4 non-haematological toxicities (as percent of patients) were asthenia (6%), vomiting (5%) and nausea (5%). No patients developed congestive heart failure.Conclusions The combination of docetaxel and epirubicin was highly active as first-line treatment for MBC and showed a manageable toxicity profile.     

SWOG S0215: a phase II study of docetaxel and vinorelbine plus filgrastim with weekly trastuzumab for HER2-positive,stage IV breast cancer

SWOG trial S0102 showed significant activity of the combination of docetaxel and vinorelbine in HER2-negative metastatic breast cancer (MBC). For HER2-positive patients, additional benefit may occur with the addition of trastuzumab due to its synergy with docetaxel and vinorelbine. Patients with HER2-positive MBC, but without prior chemotherapy for MBC or adjuvant taxane, were eligible. Docetaxel (60 mg/m²) was given intravenously on Day 1, vinorelbine (27.5 mg/m²) intravenously on Days 8 and 15, and filgrastim (5 μg/kg) on Days 2–21 of a 21-day cycle. In addition, patients received weekly infusions of trastuzumab (2 mg/kg) after an initial bolus of 4 mg/kg. The primary outcome was 1 year overall survival (OS), with secondary outcomes of progression-free survival (PFS), response rate, and toxicity. Due to slow accrual (February 2003–December 2006), enrollment was stopped after 76 of 90 planned patients. There have been 32 deaths and 51 progressions among the 74 eligible patients who received treatment. The estimated 1 year OS was 93% (95% CI 84–97%) with a median of 48 months. One-year PFS was 70% (95% CI 58–79%) with a median of 20 months. Response rate for measurable disease was 84%. No deaths were attributed to treatment. Grade 4 toxicities were reported for 19% with neutropenia the most common (15%). The most common grade 3 toxicities (33%) were leucopenia (14%) and fatigue (10%). The combination of trastuzumab, docetaxel, and vinorelbine is effective as first-line chemotherapy in HER2-positive MBC with minimal toxicity. One-year survival estimates are among the highest reported in this population.     

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.