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PubMedDate not supplied

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.

Adult↗
PubMed2006

Feasibility study comparing docetaxel-cisplatin versus docetaxel-carboplatin as first-line chemotherapy for ovarian cancer.

OBJECTIVE: To determine the feasibility of docetaxel-cisplatin combination therapy compared with docetaxel-carboplatin combination therapy as first-line chemotherapy for patients with ovarian cancer. METHODS: Fifty patients with International Federation of Gynecology and Obstetrics stage Ic-IV ovarian cancer who underwent primary surgery were randomly assigned to receive treatment with docetaxel-cisplatin (n = 23) or docetaxel-carboplatin (n = 27). Docetaxel 70 mg/m2 and cisplatin 60 mg/m2 or carboplatin to an area under the curve of 5 were administered consecutively on Day 1 of a 3-week cycle, for 3 cycles in patients with stage Ic-II cancer and for over 5 cycles in patients with stage III-IV cancer. Patients were evaluated for treatment-related toxicity in each cycle using the National Cancer Institute Common Toxicity Criteria version 2.0. RESULTS: Five patients (2 in the docetaxel-cisplatin arm and 3 in the docetaxel-carboplatin arm) discontinued the treatment at the end of the second course of chemotherapy because of apparent disease progression; however, no patients came off the protocol therapy because of treatment-related toxicity. Overall, 103 cycles of docetaxel-cisplatin treatment and 130 cycles of docetaxel-carboplatin treatment were delivered. The major toxicity was neutropenia in both regimens. The total incidence of grades 3 and 4 neutropenia was 83% (19/23) in the docetaxel-cisplatin arm and 96% (26/27) in the docetaxel-carboplatin arm. The incidence of grade 4 neutropenia was significantly lower in the docetaxel-cisplatin arm [39% (9/23) versus 74% (20/27)]. CONCLUSION: Docetaxel-cisplatin combination therapy may be feasible as first-line chemotherapy for patients with ovarian cancer.

Adult↗
PubMed2006

Interleukin 6, a nuclear factor-kappaB target, predicts resistance to docetaxel in hormone-independent prostate cancer and nuclear factor-kappaB inhibition by PS-1145 enhances docetaxel antitumor activity.

PURPOSE: To investigate whether nuclear factor kappaB (NF-kappaB)/interleukin 6 (IL-6) was linked to docetaxel response in human prostate cancer cell lines, and whether inhibition of NF-kappaB sensitized tumor cells to docetaxel. We also aimed to correlate IL-6 (as a surrogate marker of NF-kappaB) and docetaxel response in hormone-independent prostate cancer (HIPC) patients. EXPERIMENTAL DESIGN: Hormone-dependent (LNCaP) and hormone-independent (PC-3 and DU-145) prostate cancer cell lines were exposed to docetaxel alone or combined with the NF-kappaB inhibitor PS-1145 (an inhibitor of IkappaB kinase-2). Effects of dose, exposure time, and schedule dependence were assessed. Activation of NF-kappaB was assayed by electrophoresis mobility shift assay and luciferase reporter assay, IL-6 levels by ELISA, and cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle and apoptosis were assessed by fluorescence-activated cell sorting analysis. Apoptosis was also measured by detection of cleavage of poly(ADP-ribose) polymerase. In patients with metastatic HIPC receiving docetaxel-based chemotherapy, IL-6 serum levels were assayed before chemotherapy and every 3 to 4 weeks thereafter. RESULTS: PC-3 and DU-145 cells had higher NF-kappaB activity, secreted more IL-6, and were more resistant to docetaxel than LNCaP cells. NF-kappaB activity was induced by docetaxel. Cotreatment with docetaxel and PS-1145 prevented docetaxel-induced NF-kappaB activation, reduced IL-6 production, and increased docetaxel effects on cell viability in PC-3 and DU-145 cells but not in LNCaP. Synergism with docetaxel and PS-1145, as assayed by median-effect principle, was observed in DU-145 and PC-3. In HIPC patients, pretreatment IL-6 serum levels correlated to prostate-specific antigen (PSA) response: median IL-6 level was 10.8+/-9.5 pg/mL in PSA responders versus 36.7+/-20.8 pg/mL (P=0.006) in nonresponders. A PSA response was also linked to a decline in IL-6 levels during treatment. Median overall survival was 6.8 months in patients with high IL-6 versus 16.6 months in those with low IL-6 (P=0.0007). On multivariate analysis, pretreatment IL-6 (P=0.05) was an independent prognostic factor for time to disease progression and survival. CONCLUSIONS: Inhibition of NF-kappaB emerges as an attractive strategy to enhance docetaxel response in prostate cancer. The interest of this view is further supported by a significant association between high IL-6 in sera of HIPC patients and decreased response to docetaxel.

Aged↗
PubMed2000

Phase I/II dose escalation study of docetaxel and carboplatin combination supported with amifostine and GM-CSF in patients with incomplete response following docetaxel chemo-radiotherapy: additional chemotherapy enhances regression of residual cancer.

Taxanes have been shown to interact with anti-apoptotic proteins. In the present study we investigated whether the addition of taxane in combination with DNA damaging drugs can further enhance tumor shrinkage in cases with incomplete response to radiotherapy. Since the dose of docetaxel in combination with carboplatin is not known, the above hypothesis was tested in the context of a dose escalation phase I study. Twenty-eight patients with locally advanced chest or pelvic tumors, showing residual disease on CT scans performed 40 d following docetaxel radio-chemotherapy, were recruited in a dose escalation protocol of docetaxel/carboplatin supported with amifostine and GM-CSF. The starting dose of docetaxel was 40 mg/m2 every 2 weeks. Carboplatin dose was calculated using the Calvert formula and was escalated in cohorts of 4 patients (starting dose AUC2 every two weeks; AUC0.5 increments up to AUC3). Thereafter the docetaxel dose was increased to 50 and 60 mg/m2, while carboplatin was escalated (by AUC0.5 increments) starting from AUC3 and AUC4 respectively. Amifostine (600 mg/m2) was administered i.v. before carboplatin and GM-CSF (480 microg) was injected s.c. on days 5, 6 and 10, 11 of each cycle. Six cycles were given and response was assessed 2 weeks after the end of chemotherapy. None out of four patients treated in the 6th dose level cohort (50 mg/m2 of docetaxel and AUC4 of carboplatin every 2 weeks) showed any grade 2-4 hematologic toxicity. Mild non-hematologic toxicity such as neuropathy, leg edema, pleural effusion, pyrexia, alopecia grade 2 and hypersensitivity was observed in 4-12% of patients. Out of four patients treated in a 7th cohort (docetaxel 60 mg/m2 and carboplatin AUC4), one developed grade IV neutropenia and two developed grade 3 severe asthenia requiring treatment delay for 2 weeks. Out of 11 patients with PR following docetaxel radio-chemotherapy, 7 (63%) showed CR after docetaxel/carboplatin additional chemotherapy. Eight out of 17 patients with MR following docetaxel radio-chemotherapy showed PR (47%) and one showed CR (6%) after additional chemotherapy. High dose combined docetaxel (50 mg/m2) and carboplatin (AUC4) chemotherapy can be safely administered on a two-weekly basis if supported with amifostine and GM-CSF. Such an additional therapy may be important in patients with incomplete response after chemo-RT. Broad spectrum cytoprotection with amifostine and GM-CSF may also contribute to the reduction of incidence of neurosensory reactions and asthenia in patients treated with taxanes.

Adult↗
PubMed2001

Preclinical mechanisms of action of docetaxel and docetaxel combinations in prostate cancer.

Docetaxel, a semisynthetic taxane, has exhibited significant single-agent activity against prostatic tumors. In phase I/II studies, single-agent docetaxel and the combination of docetaxel plus estramustine were effective in inducing prostate-specific antigen reductions of > or =50% in men with androgen-independent prostate cancer (AIPC). The underlying reason for docetaxel's clinical activity against prostate cancer has been a focus of ongoing research. Docetaxel is believed to have a twofold mechanism of antineoplastic activity: (1) inhibition of microtubular depolymerization, and (2) attenuation of the effects of bcl-2 and bcl-xL gene expression. Taxane-induced microtubule stabilization arrests cells in the G(2)M phase of the cell cycle and induces bcl-2 phosphorylation, thereby promoting a cascade of events that ultimately leads to apoptotic cell death. In preclinical studies, docetaxel had a higher affinity for tubulin and was shown to be a more potent inducer of bcl-2 phosphorylation than paclitaxel. Laboratory evidence also supports the clinical evaluation of docetaxel-based combinations that include agents such as trastuzumab and/or estramustine. The pathways for docetaxel-induced apoptosis appear to differ in androgen-dependent and androgen-independent prostate cancer cells. Further elucidation of these differences will be instrumental in designing targeted regimens for the treatment of localized and advanced prostate cancer.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Physico-chemical stability of docetaxel premix solution and docetaxel infusion solutions in PVC bags and polyolefine containers.

We assessed the physical and chemical stability of docetaxel infusion solutions. Stability of the antineoplastic drug was determined 1.) after reconstitution of the injection concentrate and 2.) after further dilution in two commonly used vehicle-solutions, 0.9% sodium chloride and 5% dextrose, in PVC bags and polyolefine containers. Chemical stability was measured by using a stability-indicating HPLC assay with ultraviolet detection. Physical stability was determined by visual inspection. The stability tests revealed that reconstituted docetaxel solutions (= premix solutions) are physico-chemically stable (at a level > or = 95% docetaxel) for a minimum of four weeks, independent of the storage temperature (refrigerated, room temperature). Diluted infusion solutions (docetaxel concentration 0.3 mg/ml and 0.9 mg/ml), with either vehicle-solution, proved physico-chemically stable (at a level > or = 95% docetaxel) for a minimum of four weeks, when prepared in polyolefine containers and stored at room temperature. However, diluted infusion solutions exhibited limited physical stability in PVC bags, because docetaxel precipitation occurred irregularly, though not before day 5 of storage. In addition, time-dependent DEHP-teaching from PVC infusion bags by docetaxel infusion solutions must be considered.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Comparison of docetaxel and docetaxel-irinotecan combination as second-line chemotherapy in advanced non-small-cell lung cancer: a randomized phase II trial.

BACKGROUND: The aim of this study was to evaluate whether docetaxel (taxotere) treatment with or without irinotecan improved patient outcomes with similar toxicity in recurrent non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with recurrent platinum-refractory NSCLC with Eastern Cooperative Oncology Group performance status of 0-2 were randomized to either docetaxel 30 mg/m(2) and irinotecan 60 mg/m(2) (days 1 and 8) or docetaxel 75 mg/m(2) (day 1), both administered every 3 weeks. RESULTS: A total of 130 patients were randomized. The response rate (RR) (20% versus 14%), overall survival (6.5 months versus 6.4 months) and 1-year survival (37% versus 34%) were similar in the combination and docetaxel arms, respectively. The combination arm demonstrated a longer time to tumor progression (TTP) (5.6 versus 4.8 months; P=0.065). Grade 3-4 neutropenia and anemia were similar in the combination and docetaxel arms. Grades 3-4 non-hematological toxicity (except diarrhea) was mild and was similar in the two groups. Grade 3-4 thrombocytopenia (17% versus 6%; P=0.04) and diarrhea (12% versus 3%; P=0.05) occurred more frequently in the combination arm. CONCLUSIONS: The administration of irinotecan with docetaxel in platinum-refractory NSCLC prolonged TTP, but did not improve significantly RR, median survival or 1-year survival. Second-line docetaxel monotherapy offers significant and reproducible efficacy in platinum-refractory NSCLC.

Adult↗
PubMed1995

Early clinical studies with docetaxel. Docetaxel Investigators Group.

Docetaxel has been evaluated in six phase I studies involving a total of 234 patients with a wide variety of tumour types (50% had breast or ovarian cancer). The aims of these studies were to determine the optimal dosage schedule of docetaxel for use in subsequent phase II studies, and to characterise the pharmacokinetic and tolerability profiles of docetaxel. Intravenous (i.v.) doses of docetaxel (5-115 mg/m2) were administered in various treatment schedules for a total of 790 courses. Cycles were repeated every 2-3 weeks. Dose-dependent neutropenia was the major dose-limiting adverse effect of docetaxel. Other adverse events reported included hypersensitivity, fluid retention, skin reactions, asthenia and alopecia. Anaphylactoid reactions occurred rarely. No abnormal cardiac activity was detected, and neurological adverse events were mild. Docetaxel 100 mg/m2 administered as a 1 h i.v. infusion every 3 weeks combined acceptable tolerability with complete neutropenic recovery. This dosage schedule was thus considered to be optimal for further investigation in phase II studies.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Sequential two-line strategy for stage IV non-small-cell lung cancer: docetaxel-cisplatin versus vinorelbine-cisplatin followed by cross-over to single-agent docetaxel or vinorelbine at progression: final results of a randomised phase II study.

BACKGROUND: This phase II trial compared docetaxel-cisplatin (DC) with vinorelbine-cisplatin (VC), both as first-line therapy followed by cross-over at progression to single-agent vinorelbine or docetaxel in advanced non-small-cell lung cancer (NSCLC). METHODS: Overall, 115 patients received DC (docetaxel 75 mg/m(2) and cisplatin 100 mg/m(2) both on day 1, every 3 weeks, arm A1) and 118 VC (vinorelbine 30 mg/m(2)/week on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, arm B1) for six cycles, and subsequently maintained by monotherapy with docetaxel (A1) or vinorelbine (B1) with cross-over on disease progression to vinorelbine 30 mg/m(2) days 1 and 8 (A2), or docetaxel 100 mg/m(2), day 1, both every 3 weeks (B2). The primary end point was overall response rate (ORR). RESULTS: Patient characteristics were balanced; median follow-up was 8.8 months. First-line response rate was 33.9% with DC and 26.3% with VC (P=0.20). In arms A1 and B1, respectively: duration of response was similar (8.2 versus 8.4 months); median time to progression was 5 months in both; median survival was 8 versus 9 months (P=0.38); 1-, 2- and 3-year survival was 36% versus 35%, 17% versus 10% and 13% versus 6% (P not significant). However, with a low number of long-term survivors, statistical significance was not reached. Overall, almost half of the patients crossed over to second-line therapy; there were no response with vinorelbine and 6 (11.2%) partial responses with docetaxel. Considering the safety profile, the occurrence of febrile neutropenia was 9.6% with DC and 26.3% with VC. Treatment-related mortality was 2.5% with DC and 8.5% with VC. CONCLUSIONS: The trend in favour of the DC arm in ORR, even though statistical significance was not reached, is consistent with previous reports. This study suggests an activity of first-line DC in advanced NSCLC, and that second-line vinorelbine does not provide additional clinical benefit. As already shown in other studies, the use of DC in first-line should provide a better percentage of long-term survivors, despite the absence of efficacy of the second-line in our study.

Adult↗
PubMed1999

Docetaxel in the community setting: an analysis of 377 breast cancer patients treated with docetaxel (Taxotere) in the UK. UK Study Group.

BACKGROUND: Given as first- or second-line chemotherapy docetaxel appears to have great potential in advanced breast cancer. PATIENTS AND METHODS: Three hundred and seventy-seven locally advanced or metastatic breast cancer patients received docetaxel (Taxotere) as part of a named patient programme under the care of 108 oncologists from 61 cancer units across the UK. The recommended starting dose was 100 mg/m2, but patients at higher risk of toxicity started at 75 mg/m2. All patients received corticosteroid premedication. The modal number of prior chemotherapy regimens was 2 (range 1-7). 342 patients (91%) had at least one prior anthracycline-based regimen. RESULTS: Response was graded according to the managing clinician's best judgement without formal criteria. The overall response rate (ORR) was 46% among the 331 evaluable patients. 46% among the 299 patients who were anthracycline resistant and 35% among the 82 patients who were anthracycline refractory (progressive disease being the best response obtained to the most recent anthracycline containing regimen). One hundred and ninety-three patients started at the full dose of 100 mg/m2 with an ORR of 55% and 129 started at 75 mg m2 with an ORR of 33%. In October 1997, some two years after the programme had started, 26 of 377 patients were still alive, although no complete remissions have lasted to this date. Kaplan-Meier survival analysis yielded a median survival of 194 days (95% CI: 178-218 days). Haematological parameters were checked before each course of docetaxel and additionally as clinically indicated. The safety data confirmed that docetaxel has a manageable, predictable side effect profile; 29 of 377 (7.7%) patients were hospitalised as a result of neutropenic sepsis. CONCLUSIONS: The results of this named patient programme over a two year timespan confirm that docetaxel is an effective chemotherapy option in patients with locally advanced and/or metastatic breast cancer, including an 'anthracycline refractory' population.

Adult↗
PubMed2006

SCOTROC 2A: carboplatin followed by docetaxel or docetaxel-gemcitabine as first-line chemotherapy for ovarian cancer.

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P=0.102, P=0.056, P=0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% CI: 10.5-20.6); arm B 18.1 months (95% CI: 15.9-20.3); arm C, 13.7 months (95% CI: 12.8-14.6). Neutropenia was the predominant grade 3-4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P=0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.

Adult↗
PubMed2006

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer.

This trial aimed to assess the feasibility and tumour control of concurrent chemoradiotherapy or radiotherapy alone after docetaxel-based induction chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy with docetaxel (85 mg m(-2), day 1) plus cisplatin (40 mg m(-2), days 1 and 2). Patients without disease progression on day 43 were randomised to radiotherapy (2 Gy for 5 days week(-1); total 60 Gy) alone or with docetaxel 20 mg m(-2) once weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104 were evaluable for response. After induction chemotherapy, the overall response rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were subsequently randomised to local treatment. After randomised therapy, the ORR was 53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and 14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities during induction chemotherapy and randomised therapy were grades 3-4 neutropenia and grade 3 lymphocytopenia, respectively. Docetaxel-cisplatin induction therapy followed by concurrent docetaxel and thoracic radiotherapy is a feasible treatment option, showing good clinical activity and tolerability, for locally advanced NSCLC.

Adolescent↗
PubMed1999

Phase II study of docetaxel in patients with metastatic pancreatic cancer: a Japanese cooperative study. Cooperative Group of Docetaxel for Pancreatic Cancer in Japan.

Docetaxel has been reported to show promising anti-tumour activity in pancreatic ductal cancer (PC). This study was conducted to evaluate the activity and toxicity of moderate-dose (60 mg m(-2)) docetaxel in Japanese chemo-naive patients with measurable metastatic PC. The patients had a performance status of 0-2. They received docetaxel intravenously over a 1- to 2-h period without any premedication for hypersensitivity reactions. This treatment was repeated every 3-4 weeks with dose adjustments based on the toxic effects observed. Twenty-one patients were eligible and treated with docetaxel. The median number of courses was 2 (range, 1-4). None of the patients achieved an objective response; seven showed no change and 13 showed progressive disease. In one patient, the response was not assessable because of early death. The median survival time for all patients was 118 days. The main grade 3-4 toxicities by patient were leucocytopenia (67%) and neutropenia (86%). Other grade 3-4 toxicities included anaemia (10%), thrombocytopenia (5%), nausea/vomiting (29%), anorexia (29%), GOT/GPT increase (10%), alkaline phosphatase increase (14%), malaise/fatigue (33%) and alopecia (24%). In conclusion, docetaxel, administered on this schedule, did not show significant anti-tumour activity in patients with metastatic PC.

Adult↗
PubMed2005

Docetaxel plus gemcitabine or docetaxel plus cisplatin in advanced pancreatic carcinoma: randomized phase II study 40984 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group.

PURPOSE: To define the efficacy and toxicity of docetaxel plus gemcitabine or docetaxel plus cisplatin for advanced pancreatic carcinoma. PATIENTS AND METHODS: Chemotherapy-naive patients with measurable disease and WHO performance status less than 2 were randomly assigned to receive 21-day cycles of gemcitabine 800 mg/m2 on days 1 and 8 plus docetaxel 85 mg/m2 on day 8 (arm A) or docetaxel 75 mg/m2 on day 1 plus cisplatin 75 mg/m2 on day 1 (arm B). Primary end points were tumor response and rate of febrile neutropenia grade. RESULTS: Of 96 randomly assigned patients (49 patients in arm A and 47 patients in arm B), 70 patients were analyzed for response (36 in arm A and 34 in arm B) and 89 patients were analyzed for safety (45 in arm A and 44 in arm B). Confirmed responses were observed in 19.4% (95% CI, 8.2% to 36.0%) of patients in arm A and 23.5% (95% CI, 10.7% to 41.2%) in arm B. In arm A, the median progression-free survival (PFS) was 3.9 months (95% CI, 3.0 to 4.7 months), median survival was 7.4 months (95% CI, 5.6 to 11.0 months), and 1-year survival was 30%. In arm B, the median PFS was 2.8 months (95% CI, 2.6 to 4.6 months), median survival was 7.1 months (95% CI, 4.8 to 8.7 months), and 1-year survival was 16%. Febrile neutropenia occurred in 9% and 16% of patients in arms A and B, respectively. CONCLUSION: Both regimens are well tolerated and show activity in advanced pancreatic carcinoma. The safety profile and survival analyses favor docetaxel plus gemcitabine for further evaluation.

Adult↗
PubMed2005

[Cost-effectiveness analysis of capecitabine in combination with docetaxel in comparison to docetaxel monotherapy in advanced or metastatic breast cancer in France].

Objective to estimate the cost-effectiveness ratio of adopting capecitabine/docetaxel combination therapy in place of docetaxel alone, in France, in patients with metastatic breast cancer (MBC), resistant to, or relapsing after anthracycline-containing therapy, The SO14999 trial is a multicenter trial, randomized, including 511 patients equitably divided between the two groups. In addition to efficacy data, medical resource consumption related to adverse events were also collected in this trial ("piggy-back" analysis). French cost were associated to each data in order to estimate the medical cost of the two strategies from a healthpayer perspective. Afterwards, incremental cost-effectiveness analysis was performed based on the overall survival outcome and progression free survival. The addition of capecitabine to docetaxel resulted in an increase in median survival of 90 days (442 versus 352 days; p = 0.0126) and increase in the duration of progression free survival of 58 days (186 versus 128 days; p = 0.0001) compared with docetaxel alone. The total medical cost by patient was evaluated at 11,786 on average IC95% = [10,982-12,591] in the arm in association versus 11,570 IC95% = [10,719-12,421] in the arm in monotherapy; that is to say a non-significant overcost of 216 under capecitabine (p = 0.642). Moreover, the additional cost per year of life saved was estimated at 952 and the one without progression of the disease was established at 1,198 . A combined treatment associating capecitabine and docetaxel proves to be a cost-effectiveness strategy compared with the use of docetaxel alone, in the treatment of locally advanced or metastatic breast cancer in France.

Adult↗
PubMed2006

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel-irinotecan as first-line therapy for ovarian cancer.

The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy as first-line treatment for advanced epithelial ovarian carcinoma was assessed. One hundred patients were randomised to receive four 3-weekly cycles of carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of docetaxel 100 mg m(-2) (arm A, n=51) or docetaxel 60 mg m(-2) with irinotecan 200 mg m(-2) (arm B, n=49). Neither arm met the formal feasibility criterion of an eight-cycle treatment completion rate that was statistically greater than 60% (arm A 71% (90% confidence interval (CI) 58-81%; P=0.079; arm B 67% (90% CI 55-78%; P=0.184)). Median-dose intensities were >85% of planned dose for all agents. In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to treatment-related toxicity. Grade 3-4 sensory neurotoxicity was more common in arm A (1.9 vs 0%) and grade 3-4 diarrhoea was more common in arm B (0.6 vs 3.5%). Of patients with radiologically evaluable disease at baseline, 50 and 48% responded to therapy in arms A and B, respectively; at median 17.1 months' follow-up, median progression-free survival was 17.1 and 15.9 months, respectively. Although both arms just failed to meet the formal statistical feasibility criteria, the observed completion rates of around 70% were reasonable. The addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was generally well tolerated although associated with increased gastrointestinal toxicity. Further exploratory studies of topoisomerase-I inhibitors in this setting may be warranted.

Adult↗
PubMed2000

Single-agent docetaxel in metastatic breast cancer patients pre-treated with anthracyclines and paclitaxel: partial cross-resistance between paclitaxel and docetaxel.

The purpose of this study was a retrospective analysis of docetaxel in a cohort of anthracyclines and paclitaxel pretreated patients with metastatic breast cancer. From July 1998 to June 1999, 24 consecutive patients were included for this study. The regimen consisted of docetaxel 75 mg/m2 in combination with a 3-day schedule of dexamethasone every 3 weeks until disease progression or unacceptable toxicity. The median age of patients was 53 (ranged 32-67) years with a median performance status of 2. Twenty of the 24 patients (84%) had measurable disease. The median number of organs involved was 2 (range 1-4). A total of 146 cycles chemotherapy were given with a mean of 6. There was a 25% (six of 24) overall response rate including one complete response, 37.5% stable disease and 37.5% progressive disease. The major toxicity included grade 3-4 leukopenia (41.7%) and eight episodes of infection. No treatment-related death was observed. The responders included patients refractory to or resistant to prior paclitaxel treatment. The median survival and median time to disease progression was 12 and 9 months, respectively. We conclude that docetaxel has a modest activity in breast cancer patients pre-treated with anthracyclines and paclitaxel, indicating a partial cross-resistance between paclitaxel and docetaxel.

Adult↗
PubMedDate not supplied

Doxorubicin followed by docetaxel versus docetaxel followed by doxorubicin in the adjuvant treatment of node positive breast cancer: results of a feasibility study.

BACKGROUND: Doxorubicin (A) and Docetaxel (T) are amongst the most active agents in breast cancer treatment. The impact of drug sequencing is an issue still under evaluation. OBJECTIVE: To evaluate the feasibility and tolerability of two A and T-based sequential regimens, in which the sequence of drug administration was reversed. METHODS: The study included patients pts aged < or = 70 years, with operable node positive breast cancer. Two consecutive groups of patients received one of the following regimens: 1) Sequential A-->T-->CMF: Doxorubicin 75 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by Docetaxel 100 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by i.v. CMF days 1 and 8 q4wks x 3 cycles. 2) Sequential T-->A-->CMF: same doses for Doxorubicin and Docetaxel but reverse sequence of administration, followed by oral CMF (CPA 100 mg/m2, oral, days 1-14 + MTX 40 mg/m2, i.v., days 1 and 8 + 5FU 600 mg/m2, i.v., days 1 and 8, q4wks). An analysis of treatment administration and toxicity was performed for the first six cycles of CT, in the two treatment groups. RESULTS: Group 1 with 20 patients and group 2 with 14 patients were balanced in terms of patient and tumour characteristics. There was one early treatment discontinuation in each group due to toxicity (one allergic and one skin reaction to docetaxel). Median relative dose intensity was 100% for both drugs in both groups. The most relevant side effects were (overall incidence, group 1 vs group 2): Myalgia: 45% vs 72%; Arthralgia: 15% vs 57%; Skin: 35% vs 57%; Neurosensory: 55% vs 64%; Stomatitis 65% vs 36%; conjunctivitis 25% vs 57%; Neutropenic Fever 20% vs 21% and Fatigue 80% vs 93%. Grade 3/4 adverse events' rate was low in the two groups. CONCLUSIONS: 1) Both sequences were estimated feasible due to the optimal treatment administration and limited incidence of G3-G4 side effects. 2) The concomitant use of lenograstin might partially explain the reported incidence of myalgia and arthralgia. 3) No conclusion can be drawn on the most tolerable regimen due to the limited number of patients.

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