10719 Background: Capecitabine and Vinorelbine have shown considerable activity given as single agent or in combination with other drugs. The aim of this single institution ph.II study is to evaluate the response to the combination of Capecitabine and Vinorelbine given as second line treatment in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines. Methods: The regimen consists of Capecitabine 2000 mg/m2 D1-D14 and Vinorelbine 20 mg/m2 D1,D8 q 3 weeks for six cycles. Evaluation of response was accomplished with CT scan after the third and sixth cycle. Patients with disease progression after cycle 3 are taken off protocol. Patients with gr 2/3 granulocytopenia are given G-CSF for all subsequent cycles and there is a 20% dose reduction in both drugs for patients with gr 4 granulocytopenia. Results: 30 pts have been enrolled so far; according to statistical planning the total number of accrued pts should reach 63. Median age 55 yrs (30–76), median ECOG PS 1 (0–2), pre/postmenopausal 6/24. Number of metastatic sites: 1 in 6 pts, 2 in 15 pts, 3 in 6 pts and 4 in 3 pts. A total of 146 cycles was administered. Overall response rate 50% with CR in 2 (6.7%) pts, PR in 13 (43.3%) pts. Stable disease was observed in 4 (13.3%) pts, 8 (26.6%) pts had progressive disease and 3 (10%) were non evaluable. Toxicity: anemia gr 2 in 2 (6.7%) pts and gr 3 in 1 (3.3%) ptn, thrombocytopenia gr2 in 2 (6.7%) pts, granulocytopenia gr 2/3 in 17 (56.7%) pts and gr4 in 1 (3.3%) ptn. Gr 1/2 nausea or vomiting was observed in 5 (16.6%) pts and gr 3/4 in 2 (6.7%) pts. Vinorelbine induced phlebitis in 3 (10%) pts, gr1/2 diarrhea in 3 (10%) and fungal infection of the nail beds in 2 (6.7%) pts. Conclusions: Preleminary results suggest that the Capecitabine and Vinorelbine combination is an active and safe regimen for second line metastatic breast cancer treatment. The study remains open to achieve the planned patient accrual. No significant financial relationships to disclose.

836 Background: The outcome of MBC pts pretreated with anthracycline- and docetaxel-containing regimens is extremely poor. The docetaxel/gemcitabine (D/G) combination has shown considerable activity as salvage treatment in pts with MBC. Preclinical and clinical data have also suggested an in vivo enhanced activity of the P/G combination. This single institution phase II study evaluated the efficacy and safety of P/G in pts with heavily pretreated MBC. Methods: The regimen consisted of P 130 mg/sm as 3-h infusion followed by G 1500 mg/sm as 30’infusion; both drugs administered on days 1,15 q 4 weeks for 6 cycles. G-CSF was administered on days 7–10 and 20–23 to all pts. Twenty eight pts have enrolled the trial since February 2004 with the following characteristics: median age 55 yrs (40–70), median ECOG PS 1 (0–2), pre/postmenopausal 6/22. All patients were anthracycline pretreated (18/28 as adjuvant) and had received docetaxel-based regimens as palliative (p) chemotherapy (ct); 8 pts had received 1 pct, 12 pts 2pct and 8 pts 3 pct. The number of disease sites was 1 in 12 pts (43%), 2 in 11 pts (40%) and 3 in 5 pts (17%). Response evaluation was performed every second cycle. Results: The overall response rate was 47%, with CR in 2 pts (7%) and PR in 11 pts (40%). Stable disease was observed in 6 patients and 9 patients had progressive disease. 10/13 responders had previous D-objective response, while 3/13 responders had D-resistant disease. The mean response duration was 4.5 months. The mean time to disease progression was 7 months. Hematological toxicity was manageable, with G3–4 neutropenia in 7% of pts, anemia G2 in 32%, G3 in 4% and thrombocytopenia G1–2 in 11% of pts. G1–2 nausea/vomiting was recorded in 50%, G1–2 mucositis in 18%, G1–2 skin toxicity 15% and G1–2 peripheral neurotoxicity in 29%. No cardiotoxicity was observed. Conclusions: Preliminary results of this ongoing trial suggest that the combination of biweekly P/G combination is an effective and well tolerated regimen as salvage treatment for MBC pts. No significant financial relationships to disclose.

BACKGROUND:Trastuzumab has been repeatedly shown to result in significant clinical benefits and was subsequently accepted as the treatment of choice for HER2-positive advanced breast cancer - particularly as first-line treatment in combination with taxanes and as monotherapy in the second-line or third-line setting. Trastuzumab is currently licensed as a weekly treatment, although a 3-weekly schedule could be used conveniently in combination with other cytotoxic agents that are administered on a 3-weekly basis in metastatic breast cancer.PATIENTS AND METHODS:We determined the safety of i.v. trastuzumab (8 mg/kg followed by 6 mg/kg) every 3 weeks in combination with chemotherapeutic agents administered in 3-weekly courses (docetaxel, vinorelbine and capecitabine) in 31 patients with HER2-positive recurrent locoregional and/or metastatic breast cancer.RESULTS:3-weekly trastuzumab appeared to be as well tolerated as the standard once-weekly schedule. All myelosuppressive adverse events and the majority of non-hematological adverse events were typical and characteristic of the individual concomitant cytotoxic agents. Transient trastuzumab-related infusion reactions occurred in 5 patients and 1 patient developed cardiac dysfunction, which recovered after discontinuation of trastuzumab. Efficacy appeared favourable: 18 clinical responses (3 complete and 15 partial) and 8 disease stabilizations gave an overall response rate of 58% (70% in the 20 patients receiving first-line therapy). Median progression-free and overall survival times were 9.9 months (95% CI: 6.3-13.5) and 23.1 months (95% CI: 19.2-27.0), respectively.CONCLUSIONS:These findings will likely encourage further evaluation of this more convenient 3-weekly trastuzumab regimen in patients with HER2-positive metastatic breast cancer.

This paper reports the case of a 45-year-old female with histologically documented, multiple cutaneous metastases in the palmar and plantar surface of the fingers and toes originating from a breast adenocarcinoma after treatment with a docetaxel and pegylated liposomal doxorubicin regimen. The rarity of such a metastatic pattern from breast cancer and the eventual association with the chemotherapy administered are thoroughly discussed.

BACKGROUND The presence of simultaneous carcinomas involving both the ovary and uterus is relatively uncommon, while the possible link between fertility drugs and carcinogenesis still remains controversial. CASE The case of a 40-year-old patient with simultaneous aggressive endometrioid carcinoma of the ovary and uterus a few months after the sixth attempt of in vitro fertilization is presented. The patient had de novo lung disease at surgery and diffuse metastatic spread to adjacent bone, subcutaneous tissue and the central nervous system (CNS) soon after a spectacular response to the primary paclitaxel/carboplatinum chemotherapy and while on maintenance and second-line chemotherapy, respectively. CONCLUSION The fulminating course of our patient might in part be attributed to the existence of advanced disease at presentation. Definite conclusions about the possible association with the previously performed assisted reproduction cannot be drawn but close clinical surveillance of such patients before, during and after infertility treatment is strongly warranted.

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.

BACKGROUNDThe docetaxel and gemcitabine combination is active as salvage therapy in taxane-resistant/refractory patients with metastatic breast cancer (MBC). We conducted a phase II study to determine if this activity is due to an in vivo synergistic effect.PATIENTS AND METHODSWomen with measurable MBC, who were refractory or resistant to docetaxel monotherapy as first- or second-line treatment, were enrolled. Patients with progressive disease (PD) or stable disease (SD) after receiving at least four cycles of docetaxel received gemcitabine 900 mg/m(2) on days 1 and 8 plus docetaxel 100 mg/m(2 )on day 8, every 3 weeks. Granulocyte colony-stimulating factor could be used prophylactically in patients who experienced grade 3/4 neutropenia after the first cycle.RESULTSBetween January 1999 and March 2002, 173 courses of docetaxel and gemcitabine were administered to 50 patients. The median number of metastatic sites was two (range one to three). Forty-six percent of patients responded (three complete responses, 20 partial responses), whereas 28% had SD and 26% had PD. The median duration of response was 6.1 +/- 2.4 months. The median time to disease progression was 7.5 months (range 1-25) and the overall median survival was 15 months (range 3-57). Neutropenia was the only National Cancer Institute Common Toxicity Criteria grade 4 toxicity (in seven patients). Hematological grade 3 toxicities included neutropenia in 12 patients, thrombocytopenia in seven and anemia in one, while non-hematological toxicities were mild and manageable.CONCLUSIONSThe high overall response rate of the docetaxel plus gemcitabine combination after docetaxel failure in patients with MBC can be attributed to an in vivo synergism between the two drugs. These data warrant confirmation in a randomized study.

Background: The aim of this study was to determine the activity and safety of pegylated liposomal doxorubicin (PLD; Caelyx(R)) and docetaxel combination as first-line treatment in patients with metastatic breast cancer (MBC).Patients and methods: Forty-four patients with a median age of 63 years were treated with PLD 30 mg/m(2) (day 1) and docetaxel 75 mg/m(2) (day 2) every 3 weeks for six cycles. Recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF) could be used in patients with grade greater than or equal to3 neutropenia after the first cycle.Results: Forty-two of 44 patients were assessable for response. The response rate (RR) was 64.3% (95% confidence interval 49.8% to 78.8%). Six patients (14.3%) achieved complete response (complete disappearance of all measurable and assessable disease lasting at least 4 weeks, no new lesions, no disease-related symptoms), partial response was observed in 21 patients (50%) (greater than or equal to50% decrease of measureable disease lasting at least 4 weeks, no progression of assessable disease, no new lesions, no disease-related symptoms), eight patients had stable disease and seven patients progressive disease. Median disease-free and overall survival were not reached, but were in excess of 17 months (range 6-17 months). Twenty of the patients had received previous adjuvant chemotherapy (10 with epirubicin-containing regimen with a median cumulative dose of 400 mg/m(2)). Grade greater than or equal to3 neutropenia occurred in 18.4% and neutropenic fever in 9% of patients. Palmar-plantar erythro-dysesthesia was observed in four patients. Dose reduction was necessary in seven patients. Two patients discontinued treatment: one due to prolonged grade 3-4 neutropenia and one due to neurotoxicity. No treatment-related deaths occurred.Conclusions: The combination of PLD and docetaxel achieved high RRs with acceptable toxicity as first-line treatment in MBC.

842 Background: The safety profile of weekly H is well known. However, recent studies have shown that H 6mg/kg q3w is as well tolerated and maintains therapeutic H levels over 21 days. Based on these data, we have investigated H q3w plus docetaxel (T), vinorelbine (N) or capecitabine (X). Methods: 31 patients (pts) with HER2-positive (23 IHC 3+, 8 IHC2+/FISH-positive) disease were enrolled. 20 pts were treated first line (prior adjuvant chemotherapy allowed). 11 patients had received prior therapy for RBC (1–3 regimens). Drug doses: H–8mg/kg loading, 6mg/kg q3w, day (d)1; T–100mg/m2, d1; N–25mg/m2, d1/8; X–2500 mg/m2, d1–14. Treatment was discontinued or cytotoxic changed upon disease progression. Results: H was combined with T, N or X in 11, 11 and 12 patients respectively. A total of 293 courses have been given (range 3–30, median 9.45). In 2 pts, N replaced X and in one pt X replaced N upon progression. In one pt, T was given after X and N. 2 pts received H/T plus carboplatin and one received H/N plus gemcitabine. In 2 IHC2+/FISH-positive pts, treatment was discontinued after FISH reassessment (these pts were included in the toxicity evaluation). Overall, the q3w H-containing regimens were well tolerated. The majority of toxicities observed were typical of the cytotoxics administered. Five pts displayed H infusion-related reactions. One H/X pt with previous anthracycline exposure displayed a grade 2 decrease in LVEF, associated with an intraventricular clot and persistant hypokalaemia. H, but not X, was discontinued and LVEF normalised 6 months later. One H/T pt with known lymhangitic pulmonary disease had transient post-infusion dyspnea. Although, given the heterogeneity of the study, efficacy of the q3w schedule cannot be evaluated, 18 clinical responses (3 CR, 15 PR), 8 cases of stable disease and 5 of progressive disease have been documented after ≥3 courses. Median time to progression, duration of response and survival have not yet been reached. Conclusion: In this small, heterogeneous group of pts, q3w H plus chemotherapy seems to be as well tolerated and active as weekly H. No significant financial relationships to disclose.

Objectives: To evaluate the efficacy and safety of docetaxel in combination with carboplatin as salvage treatment in women with metastatic breast cancer (MBC). Patients and Methods: Chemotherapy-pretreated women with MBC were treated with docetaxel 75 mg/m2 as 1-hour i.v. infusion followed by carboplatin AUC 6 mg/ml·min, using the Calvert’s formula, as 30-min i.v. infusion. Cycles were repeated on an outpatient basis every 3 weeks. Results: Thirty-six patients received a total of 210 chemotherapy cycles (median 6 cycles/patient). All but one patient had previously received anthracyclines for the treatment of metastatic disease and half of the patients had failed to respond to front-line treatment. Twenty-eight (78%) patients had visceral disease. On an intention-to-treat analysis there were three (8%) complete and 19 (53%) partial responses for an overall response rate of 61% (95% CI: 45.2–77.0%). The response rate was 44% (2 CRs, 6 PRs) among 18 patients who had progressive or stable disease as best response to front-line treatment. The median duration of response was 8 months, the median time to tumor progression 10 months, and the probability of 1-year survival 66%. Grade 3–4 neutropenia was the main hematologic toxicity occurring in 16 (45%) patients or 36 (17%) cycles. Seven (19%) patients developed 8 (4%) febrile neutropenic episodes. Grade 3 thrombocytopenia occurred in 4 (11%) patients or 6 (3%) cycles. Non-hematologic toxicity was generally mild. G-CSF was used in 19 (53%) patients or 134 (64%) cycles. There was one sudden death possibly related to the treatment. Conclusion: The docetaxel-carboplatin combination is an active outpatient salvage regimen for the treatment of women with MBC relapsing or not responding to anthracycline-based front-line therapy.

Accessible online at: www.karger.com/ocl Effective salvage treatment is needed for patients with a good performance status and metastatic breast cancer (MBC) not responding to anthracyclines and taxanes. Capecitabine has been proven active and was well tolerated in this group [1]. However, alternative treatments are still warranted. Gemcitabine is active in MBC with response rates of 14–37 [2, 3] and 25–29% [4, 5] in chemotherapy-naive and pretreated patients, respectively. Moreover, 10–23% of pretreated MBC patients may respond to irinotecan [6, 7]. Based on the different mechanisms of action of gemcitabine and irinotecan, their distinct dose-limiting toxicities, and preclinical data showing an in vitro synergism [8], we conducted a multicenter phase II trial to assess the efficacy and toxicity of the combination in patients with MBC pretreated with both taxanes and anthracyclines.

The purpose of this study was to compare the efficacy and safety profile of docetaxel versus the combination of docetaxel/cisplatin as frontline treatment of patients with advanced or metastatic non—small-cell lung cancer (NSCLC) in a multicenter, randomized, prospective phase III trial. Patients with unresectable stage IIIB or metastatic stage IV NSCLC who had previously undergone no chemotherapy were allocated to receive either docetaxel (100 mg/m2 in a 1-hour intravenous infusion; group A) or the combination of docetaxel (100 mg/m2 day 1) and cisplatin (80 mg/m2 day 2) after adequate hydration (group B). Appropriate premedication was given before docetaxel infusion. All patients in group B received granulocyte colony-stimulating factor (150 μg/m2 subcutaneously) support from days 3 to 9 after treatment. Response and toxicity were assessed by World Health Organization criteria. From March 1999 to November 2001, 302 patients were randomly assigned to receive docetaxel (group A, n = 146) or docetaxel/cisplatin (group B, n = 156). The overall response rate was significantly higher in the combination arm (18% vs. 36%; P < 0.001). However, the 2 groups did not differ in median duration of response, time to progression (TTP), median overall survival (OS), or 1-year survival rate. Drug combination was associated with higher toxicity than single-agent therapy. Both regimens had comparable activity in terms of TTP and OS in chemotherapy-naive patients with advanced NSCLC; however, singleagent therapy had a more favorable toxicity profile.

BACKGROUND:Docetaxel in combination with cisplatin or gemcitabine are active chemotherapy reigimes against non-small-cell lung cancer. We compared the efficacy and safety of a combination of cisplatin and docetaxel (group 1) with that of gemcitabine and docetaxel (group 2) in the treatment of advanced non-small-cell lung cancer in a prospective, randomised, multicentre trial. METHODS:Patients with stage IIIB or IV lung cancer who had not had prior chemotherapy were allocated either to group 1 and treated with docetaxel (100 mg/m(2), day 1) and cisplatin (80 mg/m(2), day 2) or to group 2 and treated with gemcitabine (1100 mg/m(2), days 1 and 8) and docetaxel (100 mg/m(2), day 8). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)) had appropriate standard premedication. Response and toxicity were assessed using WHO criteria. Analysis was by intention to treat. FINDINGS:441 patients were randomly assigned to receive docetaxel/cisplatin (group 1, n=219) or gemcitabine/docetaxel (group 2, n=222). 14 patients in group 1 and 21 patients in group 2 were not evaluable. Objective response rates were similar in the two groups: group 1, 32.4% (95% CI 26.2-38.6%; 1.4% complete response and 31% partial response); group 2, 30.2% (24.5-36.2%; 0.9% complete response and 29.3% partial response). The two groups did not differ in median duration of response, time to tumour progression, overall survival, or 1 year or 2 year survival rates. INTERPRETATION:Both drug combinations had comparable activity in patients with advanced cancer who had not previously had chemotherapy; however, gemcitabine and docetaxel had the most favourable toxicity profile.

The study compares docetaxel plus cisplatin (DC) and docetaxel plus gemcitabine (DG) regimens for the treatment of advanced non-small cell lung cancer (NSCLC). Patients were randomized to receive either the DC or the DG combination. They were stratified according to age, performance status (PS) and stage of disease. Three hundred seventeen patients entered the study. Of them, 162 received the DC regimen and 155 the DG regimen. There were no differences in the patients' characteristics between the two study arms. Preliminary analysis included 132 evaluable patients in the DC arm and 114 in the DG arm. Three complete responses (CR) (2.3%) and 39 partial responses (PR) (30%) were documented in the DC arm (response rate (RR) 32.3%; 95% CI 23.87–39.76%), whereas 1 CR (0.9%) and 38 PR (33%) were documented in the DG arm (RR: 33.9%; 95% CI 25.5–42.92%). No differences in the RR, response duration, time to tumor progression, overall survival and 1-year survival were observed between the two groups. Regarding toxicity, there were no significant differences in grade 3–4 anaemia and thrombocytopenia between the two arms. However, grade 3–4 neutropenia occurred in 40 patients (33%) treated with the DC regimen and in 31 patients (22%) treated with the DG regimen (P=0.01). Twenty-four (16%) patients in the DC arm and 20 (14%) in the DG arm developed febrile neutropenia. There was one death due to sepsis in each arm. Non-haematological toxicity was mild and equal in the two arms, with the exception of grade 3–4 nausea and diarrhoea, which were more frequent in the DC arm. In conclusion, preliminary results showed that the DG regimen was as effective as the DC regimen. The toxicity profile of the DG combination was relatively milder. Hence, cisplatin cannot be considered longer as a mandatory component of chemotherapy against NSCLC.

PURPOSE:To evaluate the activity and tolerance of docetaxel in combination with mitoxantrone and granulocyte colony-stimulating factor (G-CSF) as front-line treatment in patients with metastatic breast cancer (MBC).PATIENTS AND METHODS:Fifty-four previously untreated patients with MBC who had bidimensionally measurable disease were enrolled onto the study. Forty-eight (89%) patients had visceral metastases and nineteen (36%) had relapsed within twelve months following adjuvant chemotherapy. Docetaxel (100 mg/m2) was given on day 1 after appropriate premedication and mitoxantrone (20 mg/m2) on day 8. G-CSF (150 mcg/m2/d s.c.) was administered from day 2 to day 6 and from day 9 to day 15. The regimen was repeated every three weeks, on an outpatient basis.RESULTS:In an intention-to-treat analysis, 9 (17%) CRs, 24 (44%) PRs, (overall response rate 61%; 95% confidence interval (CI): 48.1%-74.1%), 12 (22%) SD and 9 (17%) PD were observed. The median duration of response and the median time to tumor progression was 12.5 and 14 months, respectively. The overall median survival was 16.5 months, whilst the probability for one- and three-year survival was 61% and 35%, respectively. Grade 3-4 neutropenia occurred in 37 (69%) patients, and febrile neutropenia in 16 (30%); there was one death due to sepsis. Grade 3-4 thrombocytopenia occurred in four (8%) patients. Grade 2-3 neurosensory toxicity was observed in 8 (15%) patients and grade 2-3 asthenia in 24 (45%).CONCLUSIONS:Docetaxel in combination with mitoxantrone and G-CSF support is an intensified and active front-line regimen for patients with MBC; despite its hematological toxicity, this regimen merits further comparison with other standard anthracycline- and/or taxane-based combinations.