Salvage chemotherapy in anthracycline-pretreated metastatic breast cancer patients with docetaxel and gemcitabine: A multicenter phase II trial

Purpose: The activity of the docetaxel–gemcitabine combination in women with disease progression after initial chemotherapy for metastatic breast cancer (MBC) was investigated in a multicenter phase II study.Patients and methods: Fifty-two patients with metastatic breast cancer who had disease relapse or progression after completion of an anthracycline-based front-line regimen were treated with gemcitabine 900 mg/m2 on day 1 and day 8 and docetaxel 100 mg/m2 on day 8. G-CSF 150 µcg/m2/d s.c. was given from day 9 to day 16 and the treatment was repeated every three weeks. The patients' median age was 57 years and the performance status (WHO) was 0 for 26, 1 for 20 and 2 for 6 patients. The treatment was second-line for 27 (52%) and third-line for 25 (48%) patients. All patients were evaluable for response and toxicity.Results: Complete response occurred in seven (14%) patients and partial response in 21 (40%) for an overall response rate of 54% (95% confidence interval (95% CI): 40%–67%). Fifteen (29%) patients had stable disease and nine (17%) progressive disease. Of 25 patients previously treated with taxanes, 11 (44%) responded (1 CR, 10 PR). Interestingly, in four patients with disease progression while receiving docetaxel or paclitaxel monotherapy, the docetaxel + gemcitabine combination achieved partial responses. Responses were observed at all metastatic sites (local disease 62%, lymph nodes 58%, skin 44%, lung 47% and liver 36%) with a median duration of response of 3.6 months (range 1–16) and a median time to disease progression of eight months (range 2–18.5). Grade 3 neutropenia developed in 10 (19%) and grade 4 in five (10%) patients. Neutropenia was associated with infection in four patients without toxic deaths. Grade 3 thrombocytopenia developed in nine (17%) patients and grade 4 in two (4%). Non-hematologic toxicity was usually mild.Conclusion: The docetaxel–gemcitabine combination is an active and well tolerated salvage treatment in patients with MBC. Previous treatment with taxanes does not preclude a good clinical response to this regimen.     

Phase III trial of cyclophosphamide, epirubicin, fluorouracil (CEF) versus cyclophosphamide, mitoxantrone, fluorouracil (CNF) in women with metastatic breast cancer

Background: The mitoxantrone combination CNF and the epirubicin combination CEF have shown similar activity and less toxicity than the standard CAF combination in metastatic breast cancer (MBC). A prospective randomised study was started to compare safety and activity between CEF and CNF administered using a classical chemotherapeutic schedule in MBC.Patients and methods: From December 1987 to June 1993, 151 patients were randomised to receive cyclophosphamide (C) 100mgm^–2 p.o. days 1–14, fluorouracil (F) 500mgm^–2 i.v. days 1 and 8, and epirubicin (E) 30mgm^–2 i.v. days 1 and 8, or mitoxantrone (N) 6 mgm^–2 i.v. days 1 and 8, every 4 weeks. Seventythree patients were eligible for CEF and 72 for CNF.Results: Objective responses were observed in 61.6 of the CEF group and 44.4 in CNF group (p=0.004). The median duration of response was 64 weeks in CEF and 50 weeks in CNF group (p=0.02) and median time to progression was 51 and 33 weeks, respectively (p=0.0004). At the time of analysis, all except six patients (one in CNF and five in CEF) had died and the median survival time in the CEF group was longer than in CNF (74.4 weeks vs 51.4 weeks; log-rank ² test p=0.015). CNF produced more hematologic toxicity than CEF (WHO scale; grades 2–4): leucopenia 84% vs 68% (p=0.03) and trombocytopenia 17% vs 4.5% (p=0.01); CEF caused more grade 2 and 3 alopecia: 93% vs 70% (p=0.00 1).Conclusion: The combination CEF using this schedule and dosage in metastatic breast cancer is more effective with less toxicity than CNF, except for alopecia, and was associated with longer survival.     

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.     

Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer.

BACKGROUND: Women with hormone-responsive metastatic breast cancer (MBC) may respond to or have stable disease with a number of hormone therapies. We explored the efficacy and safety of the steroidal aromatase inactivator exemestane as first-line hormonal therapy in MBC in postmenopausal women. PATIENTS AND METHODS: Patients with measurable disease were eligible if they had received no prior hormone therapy for metastatic disease and had hormone receptor positive disease or hormone receptor unknown disease with a long disease-free interval from adjuvant therapy. They were randomized to tamoxifen 20 mg/day or exemestane 25 mg/day in this open-label study. RESULTS: Blinded independently reviewed response rates for exemestane and tamoxifen were 41% and 17%, respectively. Fifty-seven per cent of exemestane- and 42% of tamoxifen-treated patients experienced clinical benefit, defined as complete or partial response, or disease stabilization lasting at least 6 months. There was a low incidence of severe flushing, sweating, nausea and edema in women who received exemestane. One exemestane-treated patient had a pulmonary embolism with grade 4 dyspnea. CONCLUSIONS: Exemestane is well tolerated and active in the first-line treatment of hormone-responsive MBC. An ongoing EORTC phase III trial is comparing the efficacy, measuring time-to-disease progression, of exemestane and tamoxifen.     

Primary chemotherapy with gemcitabine, epirubicin and taxol (GET) in operable breast cancer: a phase II study

This trial was conducted to assess the activity and tolerability of the gemcitabine, epirubicin, taxol triplet combination in patients with operable breast cancer. After core biopsy, 43 women with stage II-IIIA breast cancer were treated with gemcitabine 1000 mg m(-2) over 30 min on days 1 and 4, epirubicin 90 mg m(-2) as an intravenous bolus on day 1, and taxol 175 mg m(-2) as a 3-h infusion on day 1, every 21 days for four cycles. The primary end point was the percentage of pathological complete responses (pCR) in the breast; secondary end points were tolerability, clinical response rates, overall and progression-free survival, tumour biomarkers before and after primary chemotherapy (PCT). All patients were included in safety and survival analyses; 41 eligible patients were evaluated for response. The overall clinical response rate was 87.8% (95% CI 77.8-97.8), with 26.8% complete responses (95% CI 13.3-40.3). A pCR in the breast was observed in six patients (14.6%; 95% CI 3.8-25.4); 15 patients (36.6%; 95% CI 21.9-51.3) had negative axillary lymph nodes. Grade 4 neutropenia was observed in 67.4% of the patients; febrile neutropenia occurred in 1.9% of cycles (granulocyte colony-stimulating factor was used in 3.2% of the cycles to shorten the duration of neutropenia). A statistically significant difference between Mib-1 at baseline (> or =20% in 71.4% of the patients) and at definitive surgery (28.6%, P < 0.05) was observed. The gemcitabine, epirubicin, taxol regimen is active and well tolerated as PCT for operable breast cancer. This combination allows the administration of full doses of active agents with a low incidence of febrile neutropenia.     

Randomised phase II study of epirubicin-vindesine versus mitoxantrone-vindesine in metastatic breast cancer

The purpose of this study was to compare the activity and toxicity of epirubicin-vindesine (EV) with mitoxantrone-vindesine (MV) in patients with metastatic breast cancer. A total of 295 patients was randomly allocated to treatment with vindesine 3 mg/m² combined with either epirubicin 40 mg/m² or mitoxantrone 10 mg/m². All drugs were given by intravenous push, treatment cycles were repeated at 3–4 week intervals. 255 patients were available for response, and 283 for toxicity. EV and MV yielded similar objective response rates (34 and 26%, respectively), response durations, times to progression and survival. Median time to remission was 1.8 and 3.1 months (P = 0.006) with EV and MV, respectively. In patients with visceral metastases, response rate was higher with EV than MV (40 versus 23%; P = 0.03). Patients receiving MV had less nausea/vomiting (P = 0.007) and alopecia (P = < 0.001) of WHO grade 2. Bone marrow, cardiac and other toxicities were mild with both treatments. The observed differences in activity and toxicity between the two regimens appear to have clinical relevance. EV proved to be more active in visceral disease and to be able to induce remissions more rapidly. Accordingly, patients with visceral metastases or severe tumour-related symptoms may benefit from epirubicin-based treatment. Subjective toxicities, i.e. nausea/vomiting and alopecia, were less frequent and severe with MV. Thus, MV may prove useful in patients with more indolent disease and appears to warrant phase III evaluation in such patients.     

Which benefit from adding gemcitabine to vinorelbine in elderly (>or=70 years) women with metastatic breast cancer? Early interruption of a phase II study.

BACKGROUND: Since vinorelbine and gemcitabine are both active in breast cancer with moderate toxicity, in 2002 we started a phase II trial with a combination regimen in elderly patients. PATIENTS AND METHODS: To evaluate complete plus partial response rates and toxicity of first-line vinorelbine 25 mg/m2 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 3 weeks, in women>or=70 years with advanced breast cancer and measurable lesions. All patients underwent multidimensional geriatric assessment before enrollment. A two-step design was applied, and the trial would be completed if an overall response rate>or=30% was obtained with a grade 3-grade 4 (G3-G4) toxicity rateor=70 years outside the setting of controlled clinical trials.     

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21 -day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m(-2) on day 1 and gemcitabine 1125 mg m(-2) on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26-75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35-63%). The median survival time for the patients was 42 weeks (95% CI 13-69).     

Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: A multicenter dose-escalation study

Purpose: To determine the maximum tolerable dose (MTD) and the dose-limiting toxicity (DLT) of docetaxel (D) in combination with epirubicin (Epi) in patients with advanced breast cancer.Patients and methods: Forty-seven chemotherapy-naïve metastatic breast cancer patients aged <75 years with PS (WHO) 0–2 and adequate bone marrow, renal, liver and cardiac function, were enrolled in the study. Epi was given as a five-min bolus i.v. infusion on day 1 (d1) in escalated doses with increments of 10 mg/m2; D was given in a one-hour infusion after appropriate premedication on either day 1 or on day 2 in escalated doses with increments of 10 mg/m2. The patients' median age was 60 years, 42 (89%) had a PS (WHO) 0–1, 16 (34%) were premenopausal and 25 (53%) had visceral disease.Results: When the two drugs were given on the same day, the MTD1 was reached at the doses of Epi 60 mg/m2 and D 80 mg/m2; administration of G-CSF could not result in a dose intensification. When the drugs were given on two consecutive days, the MTD2 was reached at the doses of Epi 80 mg/m2 (d1) and D 90 mg/m2 (d2). The dose-limiting events were febrile neutropenia and grade 4 neutropenia, which developed in 30 (64%) patients during the study; among 227 delivered cycles grade 3–4 neutropenia occurred in 64 (28%) cycles but only 22 (10%) of them were complicated by fever. There were no septic deaths. Grade 1–2 neurosensory toxicity occurred in nine (19%) patients, mild edema in eight (17%) and allergic reactions in five (11%). Four (9%) patients presented a greater than 10% decrease of LVEF and treatment discontinuation was required in two of them; none of the patients developed congestive heart failure. Nevertheless, one patient suddenly died 10 days after treatment initiation of myocardial ischemia, and this death is considered treatment-related. Five (14.7%) complete and thirteen (38.2%) partial responses (ORR: 53.9%; 95% confidence interval: 36.1%–69.7%) were observed in 34 evaluable patients. Ten (29.4%) and six (17.6%) patients had stable and progressive disease, respectively. The median duration of response and time to tumor progression were five and seven months, respectively. The median survival has not yet been reached.Conclusions: The combination of epirubicin and docetaxel is a feasible and well tolerated regimen, but the MTD depends on the administration schedule of the drugs.     

Monthly docetaxel and weekly gemcitabine in metastatic breast cancer: A?phase II trial

Background:Docetaxel and gemcitabine are active againstbreast cancer. The purpose of this phase II study was to evaluate theefficacy and safety of monthly docetaxel combined with weeklygemcitabine in patients with chemotherapy-pretreated metastatic breastcancer. Patients and methods:Thirty-nine patients were enrolled, ofwhom thirty had received prior chemotherapy in the adjuvant setting,seven for metastatic disease, and two for both, including prioranthracycline in 33 patients. Treatment was gemcitabine 800mg/m² days 1, 8, 15 and docetaxel 100 mg/m² on day1, with cycles repeated every four weeks. Results:Response rate was 79% (95% confidenceinterval (CI): 63%–91%), with 2 complete and 29partial responses. Twenty-five of the responders remainedprogression-free for more than six months. Median survival was 24.5months. Delivered dose intensity of gemcitabine was lower than expected(63% of planned). The predominant hematologic toxicity was grade4 neutropenia in 36 patients, complicated by fever in three patients.With the exception of asthenia, severe non-hematological toxicities wereinfrequent. Conclusions:Monthly docetaxel, combined with weeklygemcitabine, has significant but manageable hematologic toxicity.Despite frequent dose adjustments, this doublet is very active inmetastatic breast cancer, producing a high proportion of durableresponses associated with favorable survival.     

A phase II trial of a combination of pemetrexed and gemcitabine in patients with metastatic breast cancer: an NCCTG study.

PURPOSE: This phase II study was undertaken to define the efficacy and toxicity of pemetrexed in combination with gemcitabine in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients with measurable metastatic breast cancer who had previously received an anthracycline and a taxane in either the adjuvant or metastatic setting were treated with gemcitabine 1250 mg/m2 (intravenous; days 1 and 8) and pemetrexed 500 mg/m2 (intravenous; day 8) every 21 days. RESULTS: Fifty-nine patients received a median of five cycles (range one to 22) of treatment and were followed until death or for a median of 28 months (range 19.4-36.6) among living patients. Fourteen partial responses for an overall response rate of 24% [95% confidence interval (CI) 16% to 39%] were documented. Nine (15%; CI 5% to 32%) patients had stable disease for >6 months. The median survival time was 10.3 months (95% CI 8.3-18.9) and the 1 year survival rate was 49% (95% CI 38% to 64%). The median time to progression was estimated to be 3.7 months (95% CI 2.3-5.3). The most common grade 3 or 4 toxicities were neutropenia and thrombocytopenia in 83% and 27% of patients, respectively. Fourteen percent of patients experienced febrile neutropenia. Other common grade 3 or 4 non-hematological toxicities included fatigue (17%), dyspnea (15%), rash (7%) and anorexia (5%). CONCLUSIONS: The combination of pemetrexed and gemcitabine is clinically active, with an overall response rate of 24% in patients with metastatic breast cancer who have previously been treated with an anthracycline and a taxane. Myelosuppression (66% grade 4 neutropenia and 14% febrile neutropenia) was the major treatment-related toxicity observed for this combination.     

The combination of gemcitabine and vinorelbine is an active regimen as second-line therapy in patients with metastatic breast cancer pretreated with taxanes and/or anthracyclines: a phase I-II study

Purpose. To evaluate the activity and toxicity of gemcitabine and vinorelbine (GemVin), in patients with advanced breast cancer, previously treated with anthracyclines alone or with taxanes. Patients and methods. Nine patients were entered into the phase I and 50 patients were entered into the phase II study. Gemcitabine was administered beginning with the dose of 800 mg/m² and vinorelbine was given at the fixed dose of 25 mg/m², both on days 1 and 8, every 21 days. Escalated dose levels of gemcitabine were planned by increments of 200 mg/m² per level. The median age of the 50 assessable patients for the phase II study was 56.5 years (range 30–70) and median performance status (PS, ECOG score), 1 (range 0–2). The dominant sites of metastases were viscera in 40, bone in five and soft tissue in five patients. First-line chemotherapy for metastatic disease with taxanes and anthracyclines or with anthracyclines alone was administered in 36 and 14 patients, respectively. Results. The optimal schedule for the combination was gemcitabine 800 mg/m² and vinorelbine 25 mg/m². The maximum tolerated dose of gemcitabine was 1000 mg/m², with grade 4 neutropenia occurring in two cases at this dose level. Overall, 267 cycles were given to the 50 patients enrolled into the phase II (mean 5.3; range 3–9). The schedule was well tolerated: three patients experienced grade 4 neutropenia and another four patients experienced grade 3 anemia. Non-hematological toxicities were moderate. A major objective response was observed in 42% of patients (95% confidence interval (CI), 28–57%), with complete remission in four (8%) and partial response in 17 (34%) patients. The median time to progression was 6 months. Activity as well as toxicity were similar in the subgroups of the patients pretreated either with combinations of taxanes and anthracyclines or anthracyclines alone. Conclusions. The optimal GemVin schedule is an effective and well tolerated second-line therapy in patients with metastatic breast cancer pre-treated with anthracycline – based schedules or with combinations of anthracyclines and taxanes.     

Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer

Purpose: A phase III study was performed in patients with metastaticbreast cancer (MBC) to evaluate the effect on response rate and survival ofa doubling of the epirubicin dose intensity.Patients and methods: Four hundred fifty-six patients were randomisedto receive either epirubicin 100 mg/m² or 50mg/m² in combination with 5-FU (500 mg/m²) andcyclophosphamide (500 mg/m²) (FEC 100 vs. FEC 50) i.v., every21 days for a maximum of six cycles (eight in case of CR).Results: Of 456 patients, 390 were evaluable for efficacy. Objectiveresponse (CR + PR) was seen in 57% (FEC 100) vs. 41% (FEC 50)of the evaluable patients (P = 0.003). The CR rate was higher in the FEC100 arm (12% vs. 7%, P = 0.07). FEC 100 producedsignificantly higher response rates in patients with visceral localisation(50% vs. 34%, P = 0.011) and in patients with more thantwo metastatic organ sites (64% vs. 37%, P = 0.001).Median time to progression (7.6 vs. 7 months) and overall survival (18 monthsvs. 17 months) were similar. Myelosuppression was the principal toxic effect,with grade IV neutropenia observed in 57% of the patients treated withFEC 100 vs. 9% of those on FEC 50. Grade IV infection or febrileneutropenia were observed in 8% (FEC 100) vs. 0.4% (FEC 50), butthe incidence of septic death was the same in the two arms (two patientseach). Cardiac toxicity was similar in the two treatment groups, with5% vs. 3% of the patients taken off study due to cardiac events,primarily due to a decline in LVEF. Only three patients (two in FEC 100)experienced congestive heart failure.Conclusion: This trial shows that FEC with epirubicin at 100mg/m² can be administered for repeated cycles without bonemarrow support with increased, though acceptable, toxicity and with asignificant increase of antitumor effect (especially in visceral and/orhigh-burden disease), but no increased survival.     

Pegylated liposomal doxorubicin and gemcitabine in the front-line treatment of recurrent/metastatic breast cancer: a multicentre phase II study

This multicentre phase II study was aimed at investigating the activity and safety of pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) as front-line therapy in a large series of chemotherapy-naïve recurrent/metastatic breast cancer patients. From June 2003 to December 2006, a total of 71 recurrent/metastatic breast cancer patients were enrolled. Median age was 63 years (range=37–79), and 31 patients (43.7%) were ⩾65 years old. Patients received PLD, 25 mg m⁻², day 1, followed by GEM, 800 mg m⁻², days 1 and 8, q21. Response was evaluable in 64 cases. Eight complete (12.5%) and 17 partial responses (26.6%) were registered, with an overall response rate of 39.1%. Thirty patients (46.9%) experienced stable disease, with an overall clinical benefit of 85.9%. Median time to progression (TTP) was 11 months, whereas median overall survival (OS) was not reached. The rate of 1- and 2-year OS was 79 and 61%, respectively. A total of 443 courses were evaluable for toxicity: grade 3 and 4 neutropaenia affected 14 patients (20.3%) and 3 patients (4.3%), respectively. Grade 3 and 4 palmar-plantar erythrodysesthesia syndrome was documented in five cases (7.2%) and one case (1.4%), whereas grade 3 and 4 mucositis occurred in six cases (8.7%) and two cases (2.9%), respectively. Grade 2 cardiac toxicity was observed in only one case. Interestingly enough, there was no difference in the percentage and severity of either haematological or non-haematological toxicity according to the age of the patients (<65 vs ⩾65 years). We confirmed in a large, very homogenous study sample of chemotherapy-naïve recurrent/metastatic breast cancer patients the efficacy and safety of PLD/GEM combination, providing response rates, median TTP and OS values comparable with those achieved with more toxic combinations.     

Front-line treatment of advanced breast cancer with docetaxel and epirubicin: A multicenter phase II study

Purpose:In a previous phase I trial we evaluated the toxicity anddetermined the maximum tolerated doses of the docetaxel (D)–epirubicin(Epi) combination. We conducted a multicenter phase II study to evaluate theefficacy and tolerability of this regimen as front-line treatment in womenwith advanced breast cancer (ABC). Patients and methods:Fifty-four women with ABC stage IIIB (4patients) or IV (50 patients) received front-line treatment with Epi 70mg/m² on day 1 and D 90 mg/m² on day 2. The median agewas 55 years, performance status (WHO) was 0–1 in 49 patients andvisceral disease was present in 45 (83%). Results:All patients were evaluable for toxicity and 50 forresponse. In an intent-to-treat analysis complete remission was observed in5(9%) patients, partial remission in 31 (57%) (overall responserate 66%, 95% confidence interval: 54%–79%),stable disease in 9 (17%) and disease progression in 9 (17%).After a median follow-up of 11.5 months, the median duration of responses was8 months, the median time to disease progression 11.5 months and the mediansurvival has not yet been reached. The probability of one-year survival was65%. Three hundred six cycles of treatment were administered (median6 cycles per patient). Grade 3 and 4 neutropenia was observed in 8(15%) and 31 (57%) patients, respectively, and febrileneutropenia in 19 (35%). Prophylactic rh-G-CSF was used in 45(83%) patients or 226 (74%) cycles. Other hematologic ornon-hematologic toxicities were usually mild. In five (9%) patients theleft ventricular ejection fraction (LVEF) was decreased by more than10% with the treatment. Two patients died during the treatment ofrespiratory failure without associated neutropenia. Conclusions:The combination of docetaxel–epirubicin is aneffective and well tolerated front-line treatment in patients with ABC.     

Vinorelbine alternating oral and intravenous plus epirubicin in first-line therapy of metastatic breast cancer: results of a multicentre phase II study

The combination of intravenous (i.v.) vinorelbine and epirubicin is highly active in the treatment of metastatic breast cancer (MBC). In an effort to improve patient convenience, we investigated a regimen alternating i.v. and oral vinorelbine in combination with epirubicin as first-line chemotherapy of patients with MBC. In all, 49 patients with MBC received, as first-line treatment, a combination regimen consisting of i.v. vinorelbine 25 mg m(-2) plus epirubicin 90 mg m(-2) given on day 1, and oral vinorelbine 60 mg m(-2) on day 8 (or day 15 if neutrophils <1500 mm(-3)) every 3 weeks, in an open-label, multicentre phase II study. Treatment was to be repeated for a maximum of six cycles. The study population had a median age of 55 years, half of the patients had received prior adjuvant chemotherapy and 86% presented a visceral involvement. In all, 25 responses were documented and validated by an independent panel review, yielding response rates of 51% (95% CI: 36-66) in the 49 enrolled patients and 54.5% (95% CI: 39-70) in the 44 evaluable patients. Median durations of progression-free survival and survival were 8 and 20 months, respectively. Neutropenia was the main dose-limiting toxicity, but complications were uncommon, four patients having experienced febrile neutropenia and six having developed neutropenic infection. Other frequently reported adverse events included stomatitis, nausea and vomiting, which were rarely severe. No toxic death was reported. Among patients who received six cycles, global score of quality of life remained stable. This regimen alternating oral and i.v. vinorelbine in combination with epirubicin is effective and safe. Oral vinorelbine on day 8 offers greater convenience to the patient, and decreases the need for i.v. injection and reduces time spent in hospital. Therefore, oral vinorelbine is a convenient alternative to the i.v. form in combination regimens commonly used to treat MBC.     

两种方案治疗转移性乳腺癌的临床评价与药物经济学分析

  目的  从药物经济学角度对紫杉醇联合卡铂或表柔比星两种转移性乳腺癌化疗方案进行分析,为临床用药提供参考。  方法  采用成本-效果分析法对TP、TE(T:紫杉醇,P:卡铂,E:表柔比星)两种方案进行临床病例的回顾性分析比较。  结果  中位随访期为23.5(9~42)个月,TP、TE两组方案的有效率分别为78.33%和80.00%;1年、2年无进展生存率分别为43.6%和38.9%、10.8%和17.4%;1年、2年总生存率分别为80.3%和78.3%、53.2%和47.9%,两组之间无统计学差异(P>0.05)。成本-效果分析结果表明,两方案治疗成本分别为10 303.8元和13 853.3元,成本/效果比分别为131.54和173.17(P < 0.01)。化疗不良反应方面,TP组脱发发生率明显低于TE组(P < 0.01)。  结论  两方案近期与远期疗效相当,TP方案成本-效果高于TE方案,可作为晚期乳腺癌的优选方案之一。      

吉西他滨联合表柔比星治疗转移性肝癌的临床研究

目的：观察吉西他滨联合表柔比星方案治疗转移性肝癌的疗效。方法：吉西他滨1000mg／m^2,静脉滴注,30分钟滴完,第1,8天;表柔比星60mg／m^2,静脉推注,第1天,21天为～周期。连用2—3周期。结果：45例可评价疗效患者,共化疗113个周期,肿瘤完全缓解（CR）0例,部分缓解（PR）34例,稳定（SD）7例,进展（PD）4例。总有效率为64．4％,其中鼻咽癌肝转移有效率为66．7％,胰腺癌肝转移有效率为83．3％,乳腺癌肝转移有效率80％,非小细胞性肺癌肝转移有效率52．9％,胃癌肝转移有效率62．5％。结论：吉西他滨联合表柔比星治疗转移性肝癌,是安全有效的,尤其是胰腺癌及乳腺痛肝转移疗效尤为昂著。     

吉西他滨联合表柔比星治疗转移性肝癌的临床研究

目的:观察吉西他滨联合表柔比星方案治疗转移性肝癌的疗效。方法:吉西他滨1000mg/m2,静脉滴注,30分钟滴完,第1,8天;表柔比星60mg/m2,静脉推注,第1天,21天为一周期。连用2-3周期。结果:45例可评价疗效患者,共化疗113个周期,肿瘤完全缓解(CR)0例,部分缓解(PR)34例,稳定(SD)7例,进展(PD)4例。总有效率为64.4%,其中鼻咽癌肝转移有效率为66.7%,胰腺癌肝转移有效率为83.3%,乳腺癌肝转移有效率80%,非小细胞性肺癌肝转移有效率52.9%,胃癌肝转移有效率62.5%。结论:吉西他滨联合表柔比星治疗转移性肝癌,是安全有效的,尤其是胰腺癌及乳腺癌肝转移疗效尤为显著。     

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.