Gemcitabine plus Epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: a phase II

Combination chemotherapy with newer, more active drugs in patients with advanced and/or metastatic bladder cancer might show improved response rate and survival. Gemcitabine (GEM) and Epidoxorubicin (EPI) have demonstrated activity in this disease. In addition, experimental studies in vitro have shown that the two agents have additive-synergistic effects when used in combination. Our prior phase I dose-finding study in previously untreated patients with advanced or metastatic bladder cancer defined recommended doses for further trials of GEM 1000 mg/m2 and EPI 25 mg/m2 on days 1, 8 and 15 every 28 days. A phase II trial at this dose level was initiated in previously untreated patients to assess efficacy and toxicity. Eligible patients had measurable disease; Karnofsky performance status (PS) of > 40; no prior chemotherapy; and adequate bone marrow reserve, cardiac, hepatic and renal function. Thirty- one patients (22 males, 9 females) with median age of 64 (range 44-75) and median PS of 80 were accrued, and all were eligible. Twelve patients had T4N1-2 M0, 8 had lymph node only metastases, while 11 had visceral metastases (liver, bone, lung). A total of 181 cycles was administered (range 3-7 per patient). Major toxicities (WHO grade > or = 3) were: neutropenia in 5 patients, thrombocytopenia in 2 patients, and anemia in 2 patients. Three patients had febrile neutropenic episodes and only 3 patients required dose reduction. Grade 1-2 non-hematological toxicities included nausea/vomiting, stomatitis and alopecia. No cardiac toxicity was observed. Of the 30 response evaluable patients, 17 (57%) demonstrated a major response (3 complete and 14 partial) (95% CI: 39%-75%), 7 had stable disease (23%) and 6 progressed (20%). These preliminary results confirm the phase I observation that the combination of GEM--EPI is highly active in the treatment of advanced and metastatic bladder cancer with a favourable toxicity profile.     

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.     

Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase II study

To evaluate the efficacy and toxicity of irinotecan (CPT-11) in combination with raltitrexed as first-line treatment of advanced colorectal cancer (CRC). A total of 91 previously untreated patients with advanced CRC and measurable disease were enrolled in this phase II study. The median age was 62 years (range 31-77); male/female 54/37; ECOG performance status was 0 in 50 patients (55%), one in 39 (43%) and two in two (2%). Treatment consisted of CPT-11 350 mg x m(-2) in a 30-min intravenous infusion on day 1, followed after 30 min by a 15-min infusion of raltitrexed 3 mg x m(-2). Measurements of efficacy included the following: response rate, time to disease progression and overall survival. Of the 83 evaluable patients valuable to objective response, there were five complete responses (6%) and 23 partial responses (28%), for an overall response rate of 34% (95% CI: 25.9-46.5%). In all, 36 patients (43%) had stable disease, whereas 19 (23%) had a progression. The median time to progression was 11.1 months and the median overall survival was 15.6 months. A total of 487 cycles of chemotherapy were delivered with a median of five per patient. Grade 3-4 WHO toxicities were as follows: diarrhoea in 13 patients (15%), nausea/vomiting in four (4%), transaminase increase in six (7%), stomatitis in two (2%), febrile neutropenia in three (3%), anaemia in five (6%) and asthenia in three (3%). The combination CPT-11-raltitrexed is an effective, well-tolerated and convenient regimen as front-line treatment of advanced CRC.     

Results of a phase II study of pemetrexed as first-line chemotherapy in patients with advanced or metastatic breast cancer

Palliation is the primary goal in metastatic breast cancer (MBC), and safe, efficacious, new single-agent options are needed. Pemetrexed, an antifolate, inhibits several folate-dependent enzymes involved in purine biosynthesis. The primary goal of this study was to determine the objective response rate in patients with advanced or MBC given pemetrexed as a first-line, dose-dense, every 2-week chemotherapy. Women with HER2-negative advanced or MBC, without prior cytotoxic treatment for this stage of disease, were treated with intravenous pemetrexed 600 mg/m² on Day 1 of each 14-day cycle. Standard dexamethasone, folic acid, and vitamin B₁₂ premedications were given. 37 patients enrolled; 36 received ≥1 dose of pemetrexed and 35 were evaluable for response. Median age of patients was 61.4 years, 76% were hormone receptor positive (ER+ and/or PR+). Prior treatment included adjuvant chemotherapy (57%) and/or endocrine (65%). Patients received a median of 6 cycles of pemetrexed (range, 1–21). Based on 35 evaluable patients, the overall response rate (ORR) was 26% (1 CR and 8 PR), and the clinical benefit rate (CR+ PR+ stable disease [SD] ≥6 months) was 40%. Median progression-free survival (PFS) was 4.1 months (range, <1–22.4). Median overall survival (OS) was 18.9 months (range, <1–27.7). Grades 3–4 treatment-related toxicities included: neutropenia (36%), leukopenia (17%), fatigue (14%), and anemia (14%). Grade 1/2 alopecia was seen in 8% of patients. This phase II study of dose-dense, single-agent pemetrexed showed moderate activity in the first-line setting with acceptable toxicity and no significant alopecia.     

Gemcitabine as first-line therapy in patients with metastatic breast cancer: a phase II trial.

OBJECTIVES: This phase II study was conducted to evaluate the efficacy and safety of gemcitabine in patients with metastatic breast cancer (MBC). METHODS: Women with histologically or cytologically confirmed bidimensionally measurable MBC not amendable to curative surgery or radiation were eligible. Prior chemotherapy for metastatic disease was not permitted. Patients received gemcitabine 1,200 mg/m(2) on days 1, 8 and 15 for 3 weeks every 28 days for a maximum of 8 cycles. RESULTS: Thirty-nine patients, with a median age of 58 years, were enrolled. The overall response rate for the 35 evaluable patients was 37.1% (95% confidence interval [CI], 21.5-55.1%), with 2 complete responses and 11 partial responses. Median time to progression and survival were 5.1 months (95% CI, 3.5-8.8 months) and 21.1 months (95% CI, 11.0-26.9 months), respectively. Chemotherapy was well tolerated, with a median of 4 cycles completed. Grade 4 toxicities were 1 infection and 1 abnormal pulmonary function. Grade 3 neutropenia and thrombocytopenia occurred in 30.3% and 6.3% of patients, respectively. The most common grade 3 non-hematologic toxicity was nausea/vomiting (10.3%). Five of 21 patients had improved Karnofsky performance status (KPS) scores. CONCLUSION: Single-agent gemcitabine is active and well tolerated as first-line treatment in patients with MBC.     

Gemcitabine plus epirubicin plus taxol (GET) in advanced breast cancer: a phase II study*

Purpose. To investigate the activity of the combination of gemcitabine (G) plus epirubicin (E) and taxol (T), (GET), in metastatic breast cancer, to evaluate the feasibility of this regimen as induction before high dose chemotherapy and to study the pharmacokinetic interactions of these three drugs. Patients and methods. Metastatic breast cancer patients, with bidimensionally measurable disease were eligible. Treatment consisted of G 1000mg/sqm days 1 and 4 plus E 90 mg/sqm day 1 plus T 175mg/sqm/3h day 1, every 21 days. After six courses of GET, patients aged less than 60 years, in complete or partial remission or stable disease entered a programme of high dose chemotherapy (HDCT), as consolidation treatment. Results. Thirtysix patients were included in this study. Grade 4 neutropenia was observed in 64% of the patients, with four episodes of febrile neutropenia; 39% of the patients experienced mild to moderate peripheral neuropathy; grade 2 and 3 mucositis occurred respectively in 9 (25%) and 6 (17%) patients. The overall response rate to GET was 92% (95% CI, 77.53%–98.25%); CR 31% and PR 61%. After six courses of GET, 25 patients received HDCT, leading to an overall response rate of 96% with 58% CR. At a median follow up of 25 months (range 8–39), 13 out of 36 patients are progression free and 26 alive. Median progression free survival is 21 months, while median overall survival has not yet been reached. The pharmacokinetic data show that G does not influence the interactions between E and T, while gemcitabine kinetics remains unchanged. Conclusions. The results of the present study indicate that the addition of G to E plus T as front line treatment for advanced breast cancer is well tolerated with an ORR of 92%. On the basis of the high activity and interesting progression free and overall survival rates, the GET combination deserves further evaluation in randomized trials.     

Gemcitabine and oxaliplatin combination as first-line treatment for advanced pancreatic cancer: a multicenter phase II study

Purpose  Gemcitabine is the only drug approved for single-agent therapy in advanced pancreatic carcinoma (APC). Gemcitabine-based combination chemotherapy has not yet shown promising results. Methods  This multicenter phase II study enrolled previously untreated patients with locally advanced and/or metastatic pancreatic adenocarcinoma. Patients received 1,000 mg/m² gemcitabine, 100-min infusion, day 1 and 100 mg/m² oxaliplatin, 2-h infusion, day 2; q2w. The primary end point was response rate (RR). Results  Thirteen study centers enrolled 48 eligible patients of which 44 were evaluable. The RR, median overall survival, and median time to progression were 18.2%, 9.4 and 5.6 months, respectively. Sixteen patients (36.4%) experienced clinical benefit. The global quality of life scores improved by 11.71. Grade 3/4 peripheral sensory neuropathy was noted (2.1%), while the most common hematologic toxicity was anemia (grade 3/4, 6.3%). Conclusions  Gemcitabine and oxaliplatin combination chemotherapy showed a promising activity in APC patients and was well tolerated.     

Gemcitabine plus paclitaxel as first-line chemotherapy for patients with advanced breast cancer

OBJECTIVES: To assess the efficacy and tolerability of gemcitabine and paclitaxel as first-line treatment in advanced breast cancer. METHODS: Patients with histologically confirmed metastatic or metastatic plus locally advanced breast cancer received gemcitabine 1,200 mg/m(2) on days 1 and 8 and paclitaxel 175 mg/m(2) on day 1 every 21 days for 8 cycles. RESULTS: From December 1999 to August 2001, 45 patients, with a median age of 53.5 years (range, 22-77), received a total of 260 cycles. All were assessable for response and toxicity. Twenty-seven patients had prior adjuvant therapy. Hormonal receptor status was positive in 31.1% and negative in 40.0% of patients. Main metastatic sites included soft tissue (62.2%) and lung (53.3%). The objective response rate was 66.7%; complete response, 22.2%; partial response, 44.4%; stable disease, 15.6%; progressive disease, 17.8%. Median duration of response was 18 months and median time to tumor progression was 11 months. Grade 3/4 leukopenia, neutropenia, and thrombocytopenia developed in 13.3% of patients, and 15.5% developed grade 3/4 mucositis. No treatment-related deaths occurred. Median overall survival was 19 months. CONCLUSIONS: Gemcitabine plus paclitaxel is an active combination with a favorable toxicity profile as first-line treatment for patients with advanced breast cancer.     

Gemcitabine combined with epirubicin in the treatment of patients with locally advanced or metastatic breast cancer: a phase II study

This phase II study of gemcitabine and epirubicin evaluated the activity and toxicity in advanced breast cancer. Female patients with stage IIIB or IV breast cancer received gemcitabine 1000 mg/m2 and then epirubicin 15 mg/m2 on days 1, 8, and 15 of 28-day cycles. Thirty-five patients with stage IV disease, a median age of 59 years (range, 39-73), and a median Karnofsky performance status of 90 (range, 60-100) were enrolled. Fourteen (40.0%) patients received prior chemotherapy (12 adjuvant, 4 metastatic, 2 both). Of 35 evaluable patients, 10 had PR, for an overall RR of 28.6%, and 12 (34.3%) patients had SD. Median time to progression and overall survival were 5.8 months (95% CI, 3.4-9.5 months) and 17.1 months (95% CI, 11.2-19.9 months), respectively. WHO grade 3/4 neutropenia occurred in 51.5% of patients without febrile neutropenia, and grade 3 thrombocytopenia in 29.4% of patients without hemorrhage or platelet transfusions. The most common nonhematologic toxicities were grade 3 alopecia (38.2%) and nausea/vomiting (11.4%). There were no grade 4 nonhematologic toxicities. Gemcitabine plus epirubicin is active and well tolerated in patients with metastatic breast cancer. Future studies should continue to evaluate the impact of various schedules on outcome.     

Non-pegylated liposomal doxorubicin combined with gemcitabine as first-line treatment for metastatic or locally advanced breast cancer. Final results of a phase I/II trial

Doxorubicin and gemcitabine are active as single agents in breast cancer, have different mechanisms of action, and mainly have non-overlapping side effects. Dose-dependent doxorubicin-related cardiac toxicity is the principal limitation in the metastatic setting. This open, multicenter, single-arm phase I/II study assessed the safety and activity of gemcitabine in combination with non-pegylated liposomal doxorubicin (Myocet), a more cardiac-friendly anthracycline, in the first-line treatment of patients with advanced breast cancer. We aimed to determine the optimal recommended dose (RD) of gemcitabine combined with Myocet in a population, with performance status >or=2 and LVEF >or=50%. A formal phase II study was performed afterwards. A total of 53 patients were recruited. Gemcitabine 900 mg/m(2) intravenously day 1 and 8 combined with Myocet 55 mg/m(2) intravenously day 1, every 21 days, was the final RD. The principal toxicity observed was hematological, and 48% of patients developed grade 3-4 neutropenia. Other toxicities were mild and infrequent, including nausea and vomiting. There were no symptomatic cardiac events despite the fact that 36% of the patients had received prior treatment with adjuvant anthracyclines. Objective responses were observed in 51.1% of 47 evaluable patients (95% CI: 36-66%), including two complete response. In addition, 14 patients (29.8%) demonstrated stable disease. The combination of Myocet and gemcitabine at the RD is safe and has encouraging clinical activity in patients with advanced breast cancer, without apparent cardiac toxicity in anthracycline-pretreated patients. These data support further development of this combination.     

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study

The purpose of the study was to investigate the toxicity and efficacy of the combination of gemcitabine and docetaxel in untreated advanced urothelial carcinoma. Patients with previously untreated, locally advanced/recurrent or metastatic urothelial carcinoma stage-IV disease were eligible. Patients with Performance status: PS ECOG >3 or age >75 years or creatinine clearance <50 ml min(-1) were excluded. Study treatment consisted of docetaxel 75 mg m(-2) (day 8) and gemcitabine 1000 mg m(-2) (days 1+8), every 21 days for a total of six to nine cycles. A total of 31 patients with urothelial bladder cancer, 25 men and six women, aged 42-74 (median 64) years were enrolled. The majority of patients had a good PS (51.6%; PS 0). In all, 15 (48.3%) patients had locally advanced or recurrent disease only and 16 (54.8%) presented with distant metastatic spread, with multiple site involvement in 22.5%. Toxicity was primarily haematologic, and the most frequent grade 3-4 toxicities were anaemia 11 (6.7%) thrombocytopenia eight (4.9%), and neutropenia 45 (27.6%), with 10 (6.1%) episodes of febrile neutropenia. No toxic deaths occurred. A number of patients had some cardiovascular morbidity (38.7%). Nonhaematological toxicities except alopecia (29 patients) were mild. Overall response rate was 51.6%, including four complete responses (12.9%) and 12 partial responses (38.7%), while a further five patients had disease stabilisation (s.d. 16.1%). The median time to progression was 8 months (95% CI 5.1-9.2 months) and the median overall survival was 15 months (95% CI 11.2-18.5 months), with 1-year survival rate of 60%. In conclusion, this schedule of gemcitabine and docetaxel is very active and well tolerated as a first-line treatment for advanced/relapsing or metastatic urothelial carcinoma. Although its relative efficacy and tolerance as compared to classic MVAC should be assessed in a phase III setting, the favourable toxicity profile of this regimen may offer an interesting alternative, particularly in patients with compromised renal function or cardiovascular disease.     

Gemcitabine and vinorelbine as second-line treatment in patients with metastatic breast cancer: a phase II study

BACKGROUND: To evaluate the feasibility and activity of gemcitabine and vinorelbine as a second/third-line approach in patients with advanced breast cancer. METHODS: Entered into the study were 51 consecutive patients. All had been previously treated with anthracyclines. Of these 51 patients, 36 had experienced failure or relapse after one chemotherapy line for advanced disease, and 15 after two chemotherapy lines. The dominant sites of involvement were brain in 4 patients (7.8%), liver in 22 (43.2%), lung in 10 (19.6%), bone in 10 (19.6), and soft-tissue in 5 (9.8%). Treatment consisted of vinorelbine 25 mg/m(2) and gemcitabine 1000 mg/m(2) administered on days 1 and 8 every 21 days. RESULTS: The scheme was well tolerated. Grade 3/4 neutropenia was observed in 11% of patients. Grade 3 nausea and vomiting occurred in 6%, and grade 2 neurotoxicity in 6%. No patients experienced grade 3/4 alopecia. The median relative dose intensity was 94.6% (49.7-100%) and 90.0% (23.1-100%) for vinorelbine and gemcitabine, respectively. Two patients (3.9%) were not evaluable for disease response, 4 (7.8%) attained a clinical complete response, 13 (25.5%) a partial response (for an overall response rate of 33.3%, 95% coefficient interval 20.0-46.0%), 23 (45.2%) showed stable disease, and 9 (17.6%) progressed. The median time to progression of responding patients was 10.8 months, and the median overall survival of the entire population was 17.8 months. CONCLUSIONS: Vinorelbine and gemcitabine is a manageable scheme with moderate activity in pretreated patients with advanced breast cancer.     

Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer

In this phase II, multicentre trial, patients with metastatic breast cancer (MBC) were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET). The primary objective of this study was to determine the tolerability and activity in terms of complete responce (CR) and overall response rate of the GET combination in this patient population. Patients with no prior treatment for MBC, and at least one bidimensionally measurable lesion received gemcitabine 1000 mg m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1, every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were enrolled from seven Italian institutions. A total of 297 chemotherapy courses were administered with a median of six cycles patient(-1) (range 1-8). Seven patients (15%) obtained CR and 27 patients (56%) had partial responce, for an overall response rate of 71% (95% CI: 58.3-83.7). After a median follow-up of 23.7 months (range 7.0-34.4), median progression-free survival was 10.5 months (95% CI: 9.2-11.7), and median overall survival 25.9 months. The main haematological toxicity consisted of grade 3 or 4 neutropenia that occurred in 62% of cycles (22% grade 4 and 40% grade 3). The GET combination is active and well tolerated as first-line chemotherapy for MBC.     

Pegylated liposomal doxorubicin plus carboplatin in patients with metastatic breast cancer: a phase II study

BackgroundWe determined the objective response rates produced by pegylated liposomal doxorubicin (PLD) plus carboplatin with/without trastuzumab (Herceptin).Patients and methodsPatients with measurable disease were stratified by taxane treatment history and human epidermal growth factor receptor-2 status. Treatment: PLD 30 mg/m² followed by carboplatin, day 1 of each 28-day cycle; human epidermal growth factor receptor-2 (HER2)-positive patients also received trastuzumab.ResultsArm 1 received PLD plus carboplatin (N = 41 arm 1a, taxane naive; N = 42 arm 1b, taxane pretreated); Arm 2 patients received PLD plus carboplatin + Herceptin (N = 46). Overall response rates: 31%, 31%, and 56%, respectively. Median overall survival durations were not reached in arm 1a and were 13 and 33 months for arms 1b and 2. Median progression-free survival: 8, 5, 10 months, respectively. Grades 3–4 treatment-related toxic effects for arms 1a, 1b, 2, respectively, were neutropenia 22%, 31%, 35%; thrombocytopenia 34%, 26%, 17%; and fatigue 2%, 14%, 13%.ConclusionsPLD plus carboplatin has moderate antitumor activity and excellent tolerability. Herceptin and PLD plus carboplatin in HER2-positive patients have antitumor activity without significant cardiac toxicity. Toxicity results suggest that PLD can be combined with Herceptin with minimal cardiac toxicity.     

cis-platinum-based alternating non-cross-resistant chemotherapy as a first-line treatment in metastatic breast cancer. A phase II study

Exposure to multiple non-cross-resistant drugs should increase cell kill and the chance of achieving more complete and partial responses. Our earlier study in breast cancer showed that second-line CAP (cyclophosphamide, adriamycin, cis-platinum) treatment was not cross-resistant to the CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisolone) regimen and produced a 51% response rate. These facts initiated a phase II study which used an alternating CMFVP/CAP regimen. Altogether, 49 patients entered the study and 45 were evaluated (greater than 2 cycles). The CMFVP regimen consisted of cyclophosphamide (200 mg/m2 on days 1, 2, 3, 4 and 5), methotrexate (30 mg/m2 on days 2 and 4), 5-fluorouracil (500 mg/m2 on days 1, 3 and 5), vincristine (1.4 mg/m2 on days 1 and 5), and prednisolone (40 mg p.o. on days 1-5), and was alternated with the CAP schedule (300 mg/m2 cyclophosphamide on days 1, 3 and 5, 50 mg/m2 adriamycin on day 1, and 30 mg/m2 cis-platinum on days 1, 3 and 5). Overall response was high, and 37 patients out of 45 responded (82%), with a 28% CR rate (13/45). A particularly high response rate was observed in soft tissues (86%, 18/21) and visceral organs (84%, 16/19). Only 1 patient progressed (3%). The duration of remission was 4-21+ months (median, 12 months). Six of 13 CR patients were still disease free 15 months after the treatment was stopped. The duration of survival was 5-25+ months (median, 15+ months). Toxicity was moderate (myelosuppression in 53% of patients, mainly grade I-II; stomatitis in 11%, except for 100% alopecia and 90% nausea and vomiting). One drug-related death (bone marrow aplasia) was recorded. The high antitumorigenic activity of the alternating regimen used is encouraging and may call for a randomized study for the ultimate evaluation of this treatment approach.     

Gemcitabine plus vinorelbine as first-line chemotherapy in advanced nonsmall cell lung carcinoma a phase II trial

BACKGROUND: Response and survival in patients with advanced or metastatic nonsmall cell lung carcinoma (NSCLC) remain poor. As single agents, the nucleoside analog gemcitabine, and the semisynthetic vinca alkaloid vinorelbine, have been shown to be effective in NSCLC and to have a low toxicity profile. METHODS: Fifty-four chemotherapy-naive patients with NSCLC Stage IIIB (any TN3M0 or T4 any NM0) or IV (any T any NM1) were enrolled in this single-institution Phase II study. Gemcitabine 1250 mg/m(2) and vinorelbine 25 mg/m(2) were both administered on Days 1 and 8 every 3 weeks for up to 9 courses unless disease progression or severe toxicity required their discontinuation. RESULTS: Partial tumor regression was observed in 16 patients, for an overall response rate of 30% (95% confidence interval, 18.4-46.7%) on an intent-to-treat basis. The median time to progression was 5 months (range, 3-20). The median survival was 12 months (range, 5-42+); 1-year and 2-year survival rates were 49.1% and 17%, respectively. Hematologic toxicity was mild with only 11% of the patients developing Grade 3 neutropenia. None of the patients developed any Grade 4 toxicity. CONCLUSIONS: The combination of gemcitabine plus vinorelbine is feasible on an outpatient basis. The good activity and tolerability of the regimen make it a suitable candidate for further trials, using platinum-based regimens as comparators and possibly selecting elderly and less fit patients.     

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.     

Bevacizumab plus gemcitabine and oxaliplatin as first-line therapy for metastatic or locally advanced pancreatic cancer: a phase II trial

Purpose

The gemcitabine and oxaliplatin (GEMOX) has yielded among the longest progression-free survival durations in patients with advanced pancreatic cancer (APC). We postulated that adding bevacizumab would increase the effectiveness of GEMOX.

Methods

Eligible patients had stage III or IV pancreatic cancer, ECOG PS 0-2, and no prior gemcitabine. Treatment included 1,000?mg/m² intravenous gemcitabine over 100?min on day 1, 10?mg/kg intravenous bevacizumab on day 1, and 100?mg/m² oxaliplatin given on day 2. Cycles were repeated every 2?weeks. CT imaging was performed every 6?weeks.

Results

Fifty patients were enrolled: 14 had stage III disease, the remainder stage IV. Median age was 59?years. Fourty-five patients were ECOG 0-1. The grade 3?C4 toxicity rate was 94%; fatigue (47%) and nausea (40%) were frequent. One patient died after a bowel perforation; a second died of a CVA. The median PFS was 4.9?months; median survival was 11.9?months; 1?year survival was 42%. Locally advanced patients lived 12.8?months; metastatic patients lived 10.2?months. Patients developing grade 3 hypertension were more likely to have a radiologic response (P?=?.012); survival among the top and bottom quintiles of hypertension was 14.7 and 6.2?months, respectively. Survival correlated with baseline CA 19?C9 (P?=?.004) and radiologic response. The overall response rate was 36%; 34% demonstrated stable disease.

Conclusions

The GEMOX/bevacizumab regimen demonstrated an excellent median overall survival but did not meet our objective of a 14?month median survival. Toxicity was significant. We do not recommend further evaluation of this regimen.     

Weekly docetaxel and gemcitabine following docetaxel plus epirubicin or vinorelbine as first-line treatment of metastatic breast cancer: results of a multicenter phase II study

AIMS AND BACKGROUND: Sequential docetaxel and gemcitabine following initial docetaxel plus epirubicin or vinorelbine association could be worthwhile as first-line treatment of metastatic breast cancer. METHODS: Fifty-eight patients entered a phase II study that included two sequential phases. In the first phase, 36 and 22 patients previously unexposed or exposed to adjuvant anthracyclines received the association of docetaxel (75 mg/m2, day 1) with epirubicin (75 mg/m2, day 1) or vinorelbine (20 mg/m2, days 1 and 5), respectively, every 21 days for 4 courses. In the second phase, patients who had a response (R) or stable disease (SD) received docetaxel (35 mg/m2) and gemcitabine (800 mg/m2) on days 1, 8 and 15 every 28 days for 4 courses. RESULTS: In the first phase, grade > or = III neutropenia occurred in 51% and 37% of patients during docetaxel-epirubicin and docetaxel-vinorelbine, respectively. In the second phase, it occurred in the 27% and 15% of patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine, respectively. On an intention to treat basis, the complete (CR) + partial response (PR) rate to the first phase was 71%, and 22% of patients had SD, without a significant difference between the docetaxel-epirubicin and docetaxel-vinorelbine arms. After the second phase, the CR + PR rate was 65%, and 14% of patients had SD. Median time to progression and survival were 12.1 and 22.0 months, respectively, without a significant difference between patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine. CONCLUSIONS: Following an initial docetaxel-based treatment, weekly docetaxel and gemcitabine maintains high percentages of R and SD, with improved toxicity. Survival was similar in patients previously untreated and treated with adjuvant anthracyclines.