Role of pegylated liposomal doxorubicin (PLD) in epithelial ovarian cancer

Pegylated liposomal doxorubicin (PLD, Caelyx) is an emerging option for patients with recurrent ovarian carcinoma. Several phase II studies showed promising activity of PLD in recurrent ovarian cancer patients with response rate ranging from 16 to 25%. A phase III randomized trial compared PLD 50 mg/m2 day 1 every 4 weeks with Topotecan 1.5 mg/m2 daily for 5 days q 21 in recurrent ovarian cancer patients. No differences in progression free survival and overall survival were documented between treatment arms in the general population but a survival advantage was reported for platinum-sensitive subset. Our experience with PLD in the treatment of ovarian cancer is reported in this review article. Pegylated liposomal doxorubicin is effective as a second line treatment in ovarian cancer patients; comparative data are needed to establish its role in first line therapy.     

Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval

Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L.P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6–12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy.Patients and methods: A detailed analysis of subsequent therapies and survival outcomes in the overall population and in the subsets according to platinum sensitivity was therefore conducted.Results: Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), including further platinum-based regimens (49% versus 55%). Patients in the trabectedin/PLD arm received subsequent chemotherapy at a later time (median delay 2.5 months versus PLD arm). Overall survival from subsequent platinum was significantly prolonged in the partially platinum-sensitive disease subset (hazard ratio = 0.63; P = 0.0357).Conclusion: The superiority of trabectedin/PLD over single-agent PLD in OVA-301 cannot be explained by differences in the extent or nature of subsequent therapies administered to these patients. On the other hand, these exploratory analyses support the hypothesis that the enhanced survival benefits in the partially platinum-sensitive subset might be due to an extended PFI leading to longer survival with subsequent platinum.     

Trabectedin plus pegylated liposomal doxorubicin in the treatment of patients with partially platinum-sensitive ovarian cancer: current evidence and future perspectives

The effectiveness of platinum re-treatment in relapsed ovarian cancer depends on relapse-free/treatment-free intervals. Platinum agents can be effectively readministered to platinum-sensitive patients (relapsing >12 months after platinum), but efficacy is lower in partially platinum-sensitive (PPS) disease (relapsing 6–12 months after platinum). There is no clear standard treatment challenging PPS patients. Survival data in this subset with chemotherapy combinations such as pegylated liposomal doxorubicin (PLD) plus carboplatin or gemcitabine plus PLD are available from phase II trials ranging from 16 to 21 months. Recent results from OVA-301 phase III randomized trial evaluating trabectedin plus PLD showed the longest median overall survival ever reported in PPS patients (23 months). Subsequent chemotherapy (including platinum-based regimens) was administered later and survival in patients receiving third-line platinum was longer in patients treated with trabectedin plus PLD compared with those treated with PLD alone. These results suggest that prolonging platinum-free interval (PFI) with an effective non-platinum regimen improves outcome with subsequent third-line platinum treatment. An ongoing phase III trial (INOVATYON) aims to demonstrate if the results observed with trabectedin plus PLD in PPS patients are due to PFI extension, and if PFI extension with non-platinum combination prolongs response to subsequent platinum and survival in this population.     

Intertrigo-like eruption caused by pegylated liposomal doxorubicin (PLD)

Pegylated liposomal doxorubicin (PLD) is a drug whose use is increasingly common. It has been associated with a lower rate of haematologic and cardiac side effects than its nonencapsulated form. However, mucocutaneous toxicity is quite frequent and can be severe. Here we provide a case report of a patient who developed an intertrigolike eruption during treatment with PLD.     

Pegylated liposomal doxorubicin (Caelyx) in recurrent ovarian cancer

Epithelial ovarian cancer (EOC) is the most common gynaecological malignancy in the Western world and a leading cause of death. Patients with relapsed EOC are incurable and therefore the toxicity of palliative chemotherapy and effects on health-related Quality of Life are important factors. Several newer cytotoxic agents have been used in these patients. Pegylated liposomal doxorubicin (Caelyx) has a different spectrum of activity from standard doxorubicin with response rates up to 25% in these patients and a low toxicity profile. In addition it is non cross resistant with platinum compounds. In a randomised phase III trial (n=474) of Caelyx versus Topotecan there were no significant differences in response rates, time to progression, overall survival or quality of life. Patients receiving Topotecan had more side effects requiring admission to hospital. Caelyx is a valuable therapy in platinum resistant patients with an efficacy equivalent to Topotecan but at a lower cost when side-effects and admission costs are included.     

Chemotherapy with pegylated liposomal doxorubicin and cisplatin in recurrent platinum-sensitive epithelial ovarian cancer

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is the only nonplatinum agent to significantly improve survival in patients with platinum-sensitive recurrent ovarian cancer. The present study was designed to assess the efficacy and safety of PLD plus cisplatin combination therapy in these patients. METHODS: Twenty-two women (median age, 57 years) with ovarian cancer that recurred 6 months or more after standard carboplatin and paclitaxel therapy were eligible for enrollment. Cisplatin was administered intravenously as a 60-min infusion on day 1, at a single dose of 60 mg/m(2), and PLD was given intravenously as a 1-h infusion on day 2, at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. RESULTS: Hematological toxicity was mainly leucopenia/neutropenia, and this was the principal dose-limiting toxicity. Severe (grade III-IV) leucopenia/neutropenia was observed in 7 (32%) and 9 (41%) patients, respectively. Only 2 (9%) patients were complicated by febrile neutropenia. Grade III-IV anemia occurred in only 4 (18%) patients. Severe thrombocytopenia was not noted; only 5 patients (23%) had grade I-II toxicity. NO toxicity in biochemical parameters was noted. Several severe nonhematological adverse effects were managed according to standard protocols and were transient, as well as being well-tolerated. Twenty-one patients were evaluated for response. The overall response rate was 62% (13 of 21; 95% confidence interval [CI], 38%-82%), with four (19%) complete and nine (43%) partial responses. At the time of last follow-up, all of the 22 patients were alive. The median follow-up period was 8.5 months (range, 2 to 22 months). CONCLUSION: PLD combined with cisplatin at the schedule and dosage used in this study is an active and safe second-line chemotherapy regimen with acceptable and easily manageable toxicities in women with platinum-sensitive recurrent ovarian cancer.     

Cost-minimisation analysis of pegylated liposomal doxorubicin hydrochloride versus topotecan in the treatment of patients with recurrent epithelial ovarian cancer in Spain

The study consisted of a cost-minimisation analysis since the findings from a multicentre randomised phase III trial showed that pegylated liposomal doxorubicin hydrochloride was at least as efficacious as topotecan. An economic model from the Spanish hospitals perspective was constructed to compare the costs derived from the treatment using both drugs in patients with recurrent epithelial ovarian cancer who failed a first-line platinum-containing regimen. The cost evaluation included direct medical costs: drug, drug administration and costs of managing adverse events. Estimation of resources used in managing adverse events was made retrospectively through an expert panel. Results obtained per patient were: cost of drug and administration, 8647.70 euros for pegylated liposomal doxorubicin hydrochloride and 8519.94 euros for topotecan, while cost of managing adverse events was 967.02 euros in the pegylated liposomal doxorubicin hydrochloride arm and 3304.75 euros for topotecan. The total cost per patient was therefore estimated to be 9614.72 euros for pegylated liposomal doxorubicin hydrochloride and 11 824.69 euros for topotecan, showing that pegylated liposomal doxorubicin hydrochloride produces a cost saving of 2209.97 euros per patient in comparison to topotecan. Sensitivity analyses verified the robustness of the results. These findings suggest that pegylated liposomal doxorubicin hydrochloride is an efficient therapy and can be used as a cost-saving option for treatment of patients with recurrent epithelial ovarian cancer who have failed a first-line platinum-containing regimen.     

Interstitial pneumonitis induced by pegylated liposomal doxorubicin in a patient with recurrent ovarian cancer

Interstitial pneumonitis after treatment with pegylated liposomal doxorubicin (PLD) has been rarely reported. We describe herein a case of interstitial pneumonitis in a 49-year-old woman with relapsed ovarian carcinoma treated with PLD. Twenty-five days after the second administration of PLD, she presented with fever and dry cough, and chest CT scans revealed bilateral interstitial infiltrates and ground-glass opacities. She was diagnosed to have interstitial pneumonitis induced by PLD. Steroid therapy improved her symptoms.     

Use of pegylated liposomal doxorubicin in the management of platinum-sensitive recurrent ovarian cancer: current concepts

Pegylated liposomal doxorubicin (PLD) was first approved for platinum-refractory ovarian cancer in 1999 and then received full approval for platinum-sensitive recurrent disease in 2005 by the US FDA. PLD remains an important therapeutic tool in the management of recurrent ovarian cancer in 2012. Phase-II and III clinical trials of single-agent PLD in patients with platinum-sensitive recurrent ovarian cancer have reported overall mean survival times up to 29 months. Recent interest in PLD/carboplatin combination therapy for patients with platinum-sensitive recurrent ovarian cancer has been stirred from Phase-III trials reporting response rates, progressive-free survival and overall survival similar to other platinum-based combinations, but with a more favorable toxicity profile and convenient dosing schedule. Clinical trials combining PLD with poly (ADP-ribose) polymerase inhibitors, triple angiokinase inhibitors and folate receptor inhibitors are enrolling or under development and may further augment the therapeutic efficacy of PLD.     

Pegylated liposomal doxorubicin/carboplatin combination in ovarian cancer,progressing on single-agent pegylated liposomal doxorubicin

AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma (ROC), following disease progression on single agent PLD.METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years (range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve (AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were re-evaluated and responses to therapy based on computer tomography (CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS (V19).RESULTS: A median of 10 cycles (range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients.CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.     

聚乙二醇脂质体多柔比星二线治疗晚期铂类敏感型复发性卵巢癌的临床疗效观察

目的观察聚乙二醇脂质体多柔比星治疗晚期铂类敏感型复发性卵巢癌的临床疗效。方法将100例晚期铂类敏感型复发性卵巢癌患者分为观察组50例(采用聚乙二醇脂质体多柔比星+卡铂治疗)和对照组50例(采用吉西他滨+卡铂治疗)。比较两组患者的治疗效果和不良反应发生情况。结果两组患者的治疗有效率(RR)和疾病控制率(DCR)比较,差异均无统计学意义(P﹥0.05)。观察组患者中性粒细胞减少、血小板减少和恶心呕吐的发生率均低于对照组患者,手足综合征的发生率高于对照组患者,差异均有统计学意义(P﹤0.05)。结论聚乙二醇脂质体多柔比星可用于二线治疗晚期铂敏感型复发性卵巢癌,具有不良反应轻、患者依从性好的优点,值得临床推广应用。     

Real-life experience using trabectedin plus pegylated liposomal doxorubicin combination to treat patients with relapsed ovarian cancer

The goal of recurrent ovarian cancer (ROC) treatment is no longer just palliation, but prolonging survival. This is usually through administering a new line of chemotherapy at each relapse. A novel treatment sequencing strategy to achieve this is through the intercalation of an effective non-platinum alternative, in between platinum-based therapies. Trabectedin in combination with pegylated liposomal doxorubicin (PLD) has been fully available privately in the UK since 2009 for treating patients with ROC. A single institution''s experience with the trabectedin + PLD combination, as a non-platinum/non-taxane alternative, to intercalate between platinum-based therapies is reported here. To date 6 patients have been successfully treated with trabectedin + PLD at Broomfield Hospital, Chelmsford, Essex. Here we describe a new, practice-changing treatment approach in a real-life case study of a heavily-treated patient with advanced ROC treated with trabectedin + PLD at fourth-line and then subsequently rechallenged at seventh-line; with treatment continuing until disease progression.     

Phase II study of pegylated liposomal doxorubicin: Inactive in recurrent small-cell lung cancer

Purpose:Although clinical experience with liposomal doxorubicinis still limited in solid tumours, single agent Caelyx (pegylated liposomaldoxorubicin) treatment has shown promising results in AIDS-related Kaposi'ssarcoma, metastatic breast and ovarian cancer and anecdotally in other solidtumours. This is the first report of its use in small-cell lung cancer (SCLC).The objective of this multicenter phase II study was to evaluate the safety,tolerance and anti-tumour activity of Caelyx as monotherapy in patients withrecurrent SCLC. Patients and methods:A total of 14 patients with recurrent SCLCwho had not received prior treatment with doxorubicin, were accrued into thisphase II study. All patients had progressed or relapsed after first-linechemotherapy. All but one had achieved objective responses to first-linetreatment with median duration of five months (range 2–18 months) buthalf of them had experienced refractory relapses (within 3–4 months).Study treatment consisted of Caelyx 50 mg/m² (1-hour i.v infusionevery 4 weeks for 6 cycles). Results:No responses were seen but in three patients disease wasstabilised for a median of three months. The median number of cycles was 2 perpatient, with 11 of 14 patients not completing 6 cycles of Caelyx treatment.From those, five patients were removed from the study after only one cycle dueto rapid disease progression, and one was withdrawn after three cycles due toprolonged toxicity. Overall, treatment was well tolerated with no episodes ofgrade 4 toxicity and only two episodes of grade 3 toxicities: one ofthrombocytopenia and one of prolonged palmar-plantar erythrodysesthesia (PPE). Conclusions:These results demonstrate limited activity of Caelyxin this patient population, which may be related to the poor prognosticfeatures of such patients. Our findings are in agreement with previousobservations that doxorubicin-containing combinations are rarely active inplatinum/etoposide failures. However, as in other studies the favourabletoxicity profile of Caelyx is confirmed.     

A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study)

Purpose

A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan hydrochloride (CPT-11) in CPT-11/pegylated liposomal doxorubicin (PLD) combination therapy, a novel treatment regimen for platinum- and taxane-resistant recurrent ovarian cancer.

Methods

Pegylated liposomal doxorubicin was administered intravenously on day 3 at a fixed dose of 30 mg/m². CPT-11 was administered intravenously on days 1 and 15, at a dose of 50 mg/m² on both days. One course of chemotherapy was 28 days, and patients were given a maximum of six courses, with the CPT-11 dose being increased in increments of 10 mg/m² (level 1, 50 mg/m²; level 2, 60 mg/m²; level 3, 70 mg/m²; level 4, 80 mg/m²) to determine MTD and RD.

Results

During the period from April 2010 to March 2013, three patients were enrolled for each level. In the first course, no dose-limiting toxicity occurred in any of the patients. Grade 4 neutropenia was observed in two of three patients at level 4. At level 4, the antitumor effect was a partial response (PR) in two of the three patients and stable disease (SD) in one. At level 3, one of the three patients showed PR and two had SD. At level 4, the start of the next course was postponed in two of three patients. In addition, one patient at level 4 experienced hemotoxicity that met the criteria for dose reduction in the next course. The above results suggested that administration of CPT-11 at dose level 5 (90 mg/m²) would result in more patients with severe neutropenia and in more patients requiring postponement of the next course or a dose reduction. Based on the above, the RD of CPT-11 was determined to be 80 mg/m².

Conclusions

The results suggest that CPT-11/PLD combination therapy for recurrent ovarian cancer is a useful treatment method with a high response rate and manageable adverse reactions. In the future phase II study, the safety and efficacy of this therapy will be assessed at 80 mg/m² of CPT-11 and 30 mg/m² of PLD.     

A comparative economic analysis of pegylated liposomal doxorubicin versus topotecan in ovarian cancer in the USA and the UK.

BACKGROUND: Economic information is necessary for rational decision-making in health care. Many European countries require financial impact statements prior to drug approval, and many health care organizations in the USA consider cost-effectiveness when making formulary decisions. We report the findings and discuss the policy implications of an economic evaluation based on an international, randomized controlled trial of salvage therapy for epithelial ovarian cancer, wherein topotecan and pegylated liposomal doxorubicin (PLD) were found to have similar efficacy but differing toxicities. PATIENTS AND METHODS: Direct costs to the payer were estimated for 235 North American and 239 European trial participants who had relapsed or failed platinum-based therapy. Unit costs were obtained from national sources or previously reported economic analyses. Sensitivity analyses were also performed. RESULTS: Total cost per person in the topotecan arm was 12,325 dollars (95% CI 9445 dollars to 15,415 dollars; P >0.05) higher in the USA-based analysis and 2909 dollars (95% CI 779 dollars to 3415 dollars; P <0.05) higher in the UK-based analysis than for PLD. Pegylated liposomal doxorubicin was cost saving over a wide range of assumptions. The main differences (per person) in toxicity management following PLD compared with topotecan in Europe were for blood transfusions (1190 dollars versus 181 dollars, respectively) and hospitalizations (1197 dollars versus 280 dollars, respectively). In North America, differences were mainly for granulocyte colony stimulating factors (1936 dollars versus 419 dollars micro g, respectively), erythropoietin (3493 dollars versus 308 dollars, respectively) and blood transfusions (1346 dollars versus 140 dollars, respectively). CONCLUSIONS: Policy makers who evaluate pharmacoeconomic studies should consider international differences in health care delivery. Cost assessments based on information obtained from one country may not be relevant for policy makers in a different country.     

Phase II study of single-agent pegylated liposomal doxorubicin HCl (PLD) in metastatic breast cancer after first-line treatment failure

OBJECTIVES: Aim of this study was to evaluate the clinical benefit and the toxicity of pegylated liposomal doxorubicin. PATIENTS AND METHODS: Patients with metastatic breast cancer (n = 30) who failed a prior chemotherapy regimen for metastatic disease received 45 mg/m2 pegylated liposomal doxorubicin (PLD) every 4 weeks following prophylactic administration of metoclopramide (10 mg) and dexamethasone (8 mg). RESULTS: 29 of 30 patients were assessed for clinical benefit and time to progression. All patients were assessed for toxicity and analysis of overall survival. 9 patients (31%) had a partial response, and 16 patients (55%) responded with stable disease, resulting in a clinical benefit rate of 86% (n = 25). Median time to progression was 4 months (95% CI: 2.8-5.2), median duration of response was 7 months (95% CI: 4.7-8.2), and median survival was 12 months (95% CI: 6.7-17.2). Skin toxicity was the most common adverse event (30%, all < or = grade 2). Other toxicities were remarkably low in occurrence. CONCLUSION: PLD is a well-tolerated, second-line monotherapy with a high rate of clinical benefit.     

Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil): experience with long-term maintenance in responding patients with recurrent epithelial ovarian cancer.

BACKGROUND: We hypothesized that a response to pegylated liposomal doxorubicin (PLD, Caelyx/Doxil) followed by maintenance is beneficial and safe in recurrent ovarian cancer. PATIENTS AND METHODS: Sixteen patients have received PLD for more than 1 year for recurrent ovarian (14) or fallopian tube (2) cancer. All had stable disease or better responses to PLD + carboplatin (5) or topotecan (9) doublets or to PLD alone (2). PLD maintenance therapy 30-40 mg/m(2) was given every 4-8 weeks. This analysis focuses on cardiac status, overall tolerance, and time to recurrence. RESULTS: Termination of PLD was due to progression in all patients. Noteworthy was the lack of cumulative myelosuppression and, with one exception, clinical cardiac toxicity. This patient was hospitalized with cardiogenic shock and fever complicating grade 4 pancytopenia from topotecan ten months after discontinuation of PLD. Seven patients continue to receive PLD after a median of 1680 mg/m(2) (1180-2460 mg/m(2)). Four of these had documented relapses after 3-6 years on maintenance occurring in the setting of lengthening of the treatment interval. Maintenance PLD was reinstituted after 'reinduction' with a platinum. CONCLUSIONS: PLD appears to be safe as long-term maintenance in ovarian cancer and may be important for a continued response.     

Meta-analysis of trials comparing gemcitabine and pegylated liposomal doxorubicin for treatment in women with progressive or recurrent ovarian cancer

OBJECTIVE To evaluate the efficacy and adverse effects of gemcitabine versus pegylated liposomal doxorubicin in patients with progressive or recurrent ovarian cancer. METHODS We conducted a systematic literature search to identify all randomized controlled trials comparing gemcitabine and pegylated liposomal doxorubicin for progressive or recurrent ovarian cancer. Trial data were reviewed and extracted independently by 2 reviewers. We evaluated the quality of the included studies using the Handbook 5.0 recommend standards and then analyzed data by Cochrane Collaborations RevMan 5.0. RESULTS Two trials which included a total of 348 patients were analyzed. The results of meta-analysis showed that gemcitabine improved disease control rates significantly better than pegylated liposomal doxorubicin. A greater number of patients receiving gemcitabine experienced neutropenia compared with patients receiving pegylated liposomal doxorubicin; however, hand-foot syndrome and mucositis were more severe in patients receiving pegylated liposomal doxorubicin. CONCLUSION Gemcitabine provided a limited advantage compared with pegylated liposomal doxorubicin. There exists an urgent need for more high-quality, multicenter, adequate randomized, controlled clinical trials for comparing gemcitabine with pegylated liposomal doxorubicin in patients with progressive/recurrent ovarian cancer.     

Treatment of inoperable hepatocellular carcinoma with pegylated liposomal doxorubicin (PLD): results of a phase II study

Monthly intravenous pegylated liposomal doxorubicin (PLD) 50 mg m(-2), although well tolerated, showed almost no activity in this phase II study of 16 patients with advanced hepatocellular carcinoma with a response rate of 0%, stable disease 19%, median time to progression of 2.4 months, 1-year survival of 25% and median survival of 6.5 months.     

Phase II trial of pegylated liposomal doxorubicin (Caelyx) plus Gemcitabine in chemotherapeutically pretreated patients with advanced breast cancer

A phase II trial was performed to investigate the efficacy and tolerance of combined gemcitabine and liposomal doxorubicin±recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapeutically pretreated metastatic breast cancer. Thirty-four patients were entered in this trial. Chemotherapy consisted of gemcitabine and liposomal doxorubicin±G-CSF. Twenty seven patients received this regimen as 2nd line therapy, five patients as 3rd line and two patients as 4th line therapy after having failed taxane- and/or anthracycline-based chemotherapy or other drug combinations. After a median of six courses, an overall response rate of 26% (9 PR in 34 enrolled patients) was observed; 14 patients had disease stabilization (41%), and eight (24%) progressed. Three patients were not evaluable for response due to anaphylaxis after the first course and protracted thrombocytopenia. The median TTP was 7.5 months, and median overall survival was 15 months. Myelosuppression was the most frequently observed toxicity. Non-haematological side effects were generally mild to moderate. Our data suggest that gemcitabine and liposomal doxorubicin±G-CSF is an effective and fairly well tolerated regimen for chemotherapeutically pretreated patients with advanced breast cancer.