Docetaxel-based Chemotherapy In Patients Research Articles

Surface-enhanced Raman spectroscopy of serum predicts sensitivity to docetaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer

Docetaxel-based chemotherapy, as the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC), has succeeded in helping quite a number of patients to improve quality of life and prolong survival time. However, almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially. This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy (SERS). A total of 32 mCPRC patients who underwent docetaxel chemotherapy at our center from July 2016 to March 2018 were included in this study. Patients were dichotomized in prostate-specific antigen (PSA) response group ([Formula: see text]) versus PSA failure group ([Formula: see text]) according to the response to docetaxel. In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline ([Formula: see text]0) and after 1 cycle of docetaxel chemotherapy ([Formula: see text]1). Comparing Raman peaks of serum samples at baseline ([Formula: see text]0) between two groups, significant differences revealed at the peaks of 638, 810, 890 ([Formula: see text]) and 1136[Formula: see text]cm[Formula: see text] ([Formula: see text]). The prediction models of peak 1363[Formula: see text]cm[Formula: see text] and principal component analysis and linear discriminant analysis (PCA–LDA) based on Raman data were established, respectively. The sensitivity and specificity of the prediction models were 71%, 80% and 69%, 78% through the way of leave-one-out cross-validation. According to the results of five-cross-validation, the PCA–LDA model revealed an accuracy of 0.73 and AUC of 0.83.

Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index.

Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel-based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI). We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655; N = 2,887) comparing non-docetaxel- to docetaxel-containing chemotherapy. BMI (kg/m2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status. There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04). This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition-based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.

Enterocolitis in Patients with Cancer Treated with Docetaxel.

Enterocolitis is a rare, but serious gastrointestinal complication associated with docetaxel-based chemotherapy in patients with cancer. The incidence, clinical presentation and outcome of enterocolitis in patients with cancer treated with docetaxel-based chemotherapy was assessed in this study Patients and Methods: All patients treated with docetaxel for cancer between January 2010 and December 2014 at the University Hospital of Besançon were identified and their medical records reviewed. During this period, 1,227 patients received docetaxel chemotherapy and gastrointestinal events occurred in 381 (31.1%) patients. In multivariate analysis, a higher risk of gastrointestinal events was associated with a higher dose of docetaxel (≥75 mg/m2) (odds ratio(OR)=46.2; 95% confidence interval(CI)=5.4-397.0, p=0.0005) and the first cycle of docetaxel (OR=4.2; 95% CI=1.8-10.1, p=0.001). Among the 381 patients with gastrointestinal events, grade 3/4 neutropenia, diarrhea, febrile neutropenia, mucositis, nausea/vomiting, and rectal bleeding were diagnosed in 65 (17.1%), 51 (13.4%), 37 (9.7%); 12 (3.1%), seven (1.8%) and three (0.8%) patients, respectively; 54 patients (14.2%) were hospitalized. Computed tomographic scan was performed for 39 patients (10.2%). Twenty-seven patients presented radiological signs of enterocolitis. Three deaths (0.8%) related to enterocolitis were recorded. Docetaxel was resumed in 261 patients (68.5%) and the dose was reduced in 89 patients (23.4%). Docetaxel was discontinued in 120 patients (31.5%). Gastrointestinal events in patients treated with docetaxel may be a potential sign of fatal enterocolitis and require particular attention. Dose reduction at the first cycle may reduce the risk of such events.

Development of a Nomogram for Predicting Severe Neutropenia Associated With Docetaxel-Based Chemotherapy in Patients With Castration-Resistant Prostate Cancer

BackgroundNeutropenia is a major adverse event of docetaxel-based chemotherapy. The present study was undertaken to evaluate the incidence of neutropenia and to develop a nomogram for predicting Grade 4 neutropenia during the first cycle of docetaxel-based chemotherapy in patients with castration-resistant prostate cancer (CRPC). Patients and MethodsThis study included 112 patients with CRPC treated with docetaxel-based systemic chemotherapy. We evaluated the incidence and risk factors for Grade 4 neutropenia in the first cycle of chemotherapy. ResultsSixty-two of 112 patients (55.4%) developed Grade 4 neutropenia in the first cycle of docetaxel-based chemotherapy. There were significant differences in age, baseline white blood cell count, and baseline neutrophil count between patients with non-Grade 4 neutropenia and those with Grade 4 neutropenia in univariate analyses. The serum prostate-specific antigen level, hemoglobin level, creatinine, albumin, Eastern Cooperative Oncology Group performance status, metastatic sites, extent of disease, and history of external beam radiotherapy to the prostate were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.08; P = .019) and baseline neutrophil counts (OR, 0.79; P = .045) were significant independent risk factors for severe neutropenia. A nomogram and a calibration plot on the basis of these results were developed from a multivariate logistic regression analysis to predict the probability of Grade 4 neutropenia. ConclusionAge and baseline neutrophil counts were significant independent risk factors for Grade 4 neutropenia. The nomogram to predict it provides useful information for the management of patients with CRPC treated with docetaxel chemotherapy.

Androgen-deprivation therapy plus docetaxel-based chemotherapy in metastatic hormone-sensitive prostate cancer. A meta-analysis of randomized clinical trials.

188 Background: Androgen-deprivation therapy (ADT) is the standard of treatment for patients with newly diagnosed metastatic prostatic cancer. Nevertheless, recent trials have suggested a role for chemotherapy in these patients. We performed a systematic review and meta-analysis to assess the efficacy and safety of docetaxel-based chemotherapy in combination with ADT for patients with hormone-sensitive metastatic prostate cancer. Methods: Randomized clinical trials (RCT) were identified after systematic searching of electronic databases (MEDLINE, OVID and The Cochrane Central Register of Controlled Trials), as well as ASCO conference proceedings from 2010 to 2015. We included only RCT comparing ADT versus the combination of ADT plus docetaxel-based chemotherapy in patients with newly diagnosed metastatic prostate cancer. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes: overall survival (OS) and clinical progression-free survival (PFS), according to the inverse-variance method. Heterogeneity was measured using the Q and I2statistics. Results: Three RCT (n = 2 262), were included in our meta-analysis (E3805, GETUG-AFU 15 and the M1 subgroup from STAMPEDE Trial). Docetaxel-based chemotherapy plus ADT was associated with improved OS (HR: 0.74; 95% CI: 0.60-0.90; p = 0.003). The heterogeneity of these trials was moderate (Tau2: 0.02; I2: 51%; p = 0.13). Clinical PFS was also significantly better in patients receiving docetaxel-based chemotherapy (HR: 0.67; 95% CI 0.55-0.82; p = 0.0001), with moderate between-study heterogeneity detected (Tau2: 0.01; I2: 42%; p = 0.19). Different subset of patients in these trials can explain the aforementioned heterogeneity. Regarding adverse drug reactions grade 3 or higher, neutropenia was reported in a range from 36% in the GETUG-AFU 15 Trial to 12% in the STAMPEDE trial and febrile neutropenia was reported from 6.1% in the E3805 Trial to 12% in the STAMPEDE Trial. Conclusions: The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS. New trials are needed to determine which patients benefit the most from this intervention.

Impact of prior therapy with ketoconazol or abiraterone and pattern of PSA response in a cohort of patients with metastatic castrate resistant prostate cancer (mCRPC) receiving enzalutamide for postdocetaxel.

e16082 Background: Enzalutamide has proved activity in second line setting after progression to docetaxel-based chemotherapy in patients with mCRPC in a phase III trial compared to placebo. Objecti...

A randomized, double-blind, placebo-controlled, Phase II study with and without enzastaurin in combination with docetaxel-based chemotherapy in patients with castration-resistant metastatic prostate cancer

Enzastaurin is an oral serine/threonine kinase inhibitor that inhibits the beta isoform of protein kinase C and which may have therapeutic activity in prostate cancer. We explored the efficacy of docetaxel/prednisone with or without enzastaurin in patients with castration-resistant metastatic prostate cancer. A nonrandomized safety cohort consisting of 14 patients was followed by a double-blind randomized Phase II trial. Patients received standard doses of docetaxel (75 mg/m(2)) with prednisone 10 mg daily with or without 500 mg/day of enzastaurin. There was no difference in the objective response rate between the enzastaurin and placebo arms (placebo: 7 [15.2 %]; enzastaurin: 6 [15.0 %]; P = 1.00). The median PFS was 229 days for patients in the enzastaurin arm versus 213 days for the placebo arm (P = 0.524). The 1-year overall survival rates were almost identical, with 76.7 % and 75.1 % in the enzastaurin and placebo arms, respectively. Therapy was well tolerated although the combination of enzastaurin and docetaxel was more myelosuppressive than with docetaxel alone. The clinical activity of docetaxel/prednisone plus enzastaurin cannot be distinguished from docetaxel/prednisone alone, given the limitations of a randomized Phase II design. Although the toxicity profile was favorable for the enzastaurin-containing regimen, there is no compelling rationale to move this combination forward for the treatment of castration-resistant metastatic prostate cancer.

Outcomes of Third-Line Docetaxel-Based Chemotherapy in Advanced Gastric Cancer Who Failed Previous Oxaliplatin-Based and Irinotecan-Based Chemotherapies

PurposeLittle is known about outcomes in the use of third-line chemotherapy in cases of advanced gastric cancer (AGC). The primary aim of this retrospective study was to evaluate outcomes of docetaxel-based chemotherapy in patients with AGC that progressed after both oxaliplatin-based and irinotecan-based regimens.Materials and MethodsEligible patients were those with AGC who had previous chemotherapy including fluoropyrimidine and oxaliplatin as well as fluoropyrimidine and irinotecan and who received subsequent docetaxel-based chemotherapy. Thirty-five patients were retrospectively recruited from 5 medical centers in Korea. Patients received either weekly or 3 weekly with docetaxel +/- cisplatin.ResultsThirty-one out of 35 patients were evaluated for treatment response. A total of 94 cycles of chemotherapy (median, 2; range, 1 to 7) were administered. The overall response rate was 14.3%, and the disease control rate was 45.7%. The median progression-free survival (PFS) was 1.9 months (95% confidence interval [CI], 1.1 to 2.7 months). The median overall survival (OS) was 3.6 months (95% CI, 2.8 to 4.4 months). PFS and OS were significantly prolonged in patients of the Eastern Cooperative Oncology Group, with performance status of 0 or 1 in multivariate analysis (PFS: hazard ratio[HR], 0.411; 95% CI, 0.195 to 0.868; p=0.020 and OS: HR, 0.390; 95% CI, 0.184 to 0.826; p=0.014, respectively). Four of the 35 patients enrolled in the study died due to infection associated with neutropenia.ConclusionOur findings suggest that salvage docetaxel-based chemotherapy is a feasible treatment option for AGC patients with good performance status (PS), whereas chemotherapy for patients with poor PS (PS≤2) should be undertaken with caution for those who previously failed oxaliplatin- and irinotecan-based regimens.

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

BackgroundTo evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer.MethodsPatients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed.ResultsFrom February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm.ConclusionsIn this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer.Trial registrationClinicalTrials.gov NCT00540800.

Use of class III beta tubulin to predict efficacy from paclitaxel- or docetaxel-based chemotherapy in patients with advanced gastric cancer.

52 Background: To predict clinical outcome in patients with advanced gastric cancer (AGC) received paclitaxel or docetaxel based chemotherapy, we evaluated expression of class III beta tubulin (bTubIII). Methods: Expression of bTubIII was evaluated by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tumors from the primary gastric cancer. Tumors were classified as bTubIII “low” and “high” according to median of IHC score [intensity (0-3) × portion (0-100)]. The expression of bTubIII was investigated for their association with clinical outcomes of efficacy and toxicity. Results: One hundred twenty-four AGC pts who were treated with paclitaxel or docetaxel combined with an infusional 5-fluorouracil and low-dose leucovorin as first and second-line palliative chemotherapy were enrolled. Thirty-three patients (26.7%) were confirmed to have high expression of bTubIII. The patients with high expression of bTubIII showed higher disease control rate (DCR) and longer progression-free survival (PFS) than those with low expression in patients treated with paclitaxel (79.3 % vs. 57.3 %, p = 0.039, and 3.0 months vs. 1.5 months, p = 0.073). By contrast, there was no difference of DCR and PFS according to expression of bTubIII in patients treated with docetaxel. The expression of bTubIII was not associated with toxicity in both patients treated with paclitaxel or docetaxel. Conclusions: The expression of bTubIII may be a predictive marker in AGC patients received paclitaxel based chemotherapy, but not docetaxel. No significant financial relationships to disclose.

1077 Correlation of BRCA1, DAXX, TXN, TXR1 and TSP1 tumoral expression with resistance to docetaxel-based chemotherapy in patients with advanced/metastatic Non Small Cell Lung Cancer

1077 Correlation of BRCA1, DAXX, TXN, TXR1 and TSP1 tumoral expression with resistance to docetaxel-based chemotherapy in patients with advanced/metastatic Non Small Cell Lung Cancer

Evaluation of docetaxel plus estramustine in the treatment of patients with hormone‐refractory prostate cancer

To investigate the feasibility and efficacy of docetaxel-based chemotherapy in patients with hormone-refractory prostate cancer (HRPC). Forty-six consecutive HRPC patients treated between January 2003 and March 2008 were included in this analysis. Docetaxel was given at a dose of 35 mg/m(2) twice every 3 weeks and oral estramustine concurrently for three consecutive days during weeks 1 and 2 of each cycle. During each treatment week, the dose of estramustine was 1260 mg on the first day, 980 mg on the second day and 840 mg on the third day. Patients were premedicated with 4 mg twice a day of oral dexamethasone for three consecutive days. Treatment was continued until evidence of disease progression or unacceptable toxicity. Prostate-specific antigen (PSA) levels were evaluated at least once every 4 weeks. Patients received a median of three cycles of chemotherapy. Of the evaluable 46 patients, 25 (54%) had a >or=50% PSA decline and 12 (26%) had a >or=75% PSA decline. Median time to PSA progression and overall survival time were 10.1 and 27.0 months, respectively. Median follow-up was 15.0 months. Major severe toxicities were grade 3 or 4 leukopenia in five (11%) patients. Mild toxicities included grade 1 or 2 nausea in eight (17%) patients. Two patients could not continue the treatment because of interstitial pneumonitis and a gastric hemorrhage, respectively. Docetaxel plus estramustine chemotherapy represents an active and well tolerated treatment for Japanese HRPC patients.

Vinflunine (VFL) as salvage chemotherapy in hormone-refractory prostate cancer (HRPC)

16059 Background: Two randomized, phase III trials have demonstrated survival benefits for docetaxel-based chemotherapy in patients (pts) with HRPC. Though some pts retain sensitivity to this agent after completion of therapy, progression of their disease eventually occurs. To date, there is no second-line therapy with proven survival benefits. VFL is a novel vinca alkaloid with demonstrated preclinical antitumor activity in prostate cancer models, and clinical activity in several solid tumors including breast and bladder cancer. In this multicenter phase II trial, we evaluated VFL as salvage chemotherapy in HRPC. Methods: Eligibility criteria: progressive hormone-refractory metastatic or incurable localized prostate carcinoma; ECOG PS 0–2; prior docetaxel; ≤ 2 prior chemotherapy regimens; no prior anthracycline; adequate bone marrow, kidney and liver function; informed consent. All pts received: VFL 320 mg/m2 IV every 3 weeks (280 mg/m2 for pts ECOG PS 2, GFR < 60 cc/min, or prior pelvic RT). Pts were reevaluated after 2 cycles (6 weeks); responding/stable pts received 6 cycles. This study was designed to detect a response rate > 15%; 4 responses in the first 26 evaluable pts were necessary to proceed to the second stage. Results: Between May 2007 and November 2007, 35 pts were enrolled: median age, 75 years (range 52–86); ECOG 0/1/2, 6/26/3 pts; bone metastases, 33 pts (94%); measurable disease, 14 pts (40%); > 1 prior chemotherapy regimen, 23 pts (66%). Pts received VFL for a mean of 2.6 cycles (range 1–6). 27 pts were evaluable for PSA response: 1 pt had a partial response (4%), 9 pts (33%) had stable disease, and 17 pts (63%) had progression. The single PSA responder also had an objective PR. Eight pts were inevaluable (too early, 6; withdrew from study for personal reasons, 2). Most patients progressed rapidly; only 32% were progression-free at 3 months. Grade 3/4 toxicities included neutropenia (40%), fatigue (14%), dehydration (11%), anemia (9%), and abdominal pain/cramping (6%). No treatment-related deaths occurred. Conclusions: VFL has minimal activity in heavily pretreated pts with HRPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech Bristol-Myers Squibb Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, GPC Biotech, sanofi-aventis, SCRI

Progression after docetaxel‐based chemotherapy in androgen‐independent prostate cancer

To assess the clinical pattern of progression and prostate-specific antigen doubling time (PSA-DT) after exposure to docetaxel-based chemotherapy in patients with androgen-independent prostate cancer (AIPC). Fifty-five patients received docetaxel-based chemotherapy; data were collected retrospectively from three different departments. Progression was known in 44 (79%) and the PSA-DT was available in 33 patients. Of the 29 patients with soft-tissue and soft-tissue plus bone metastases, 22 (76%) developed soft-tissue progression. Among the 35 patients with bone and bone plus soft-tissue metastases, 27 (77%) had osseous progression. There was no difference between the PSA-DT at progression before and after docetaxel-based therapy (mean 3.1 vs 2.7 months, P = 0.592, Student's t-test.). However, the median (range) PSA-DT at progression after docetaxel-based therapy was 0.84 (0.3-4) months in patients with a PSA response, significantly shorter than the median of 3.1 (0.3-12) months of patients with no biochemical response (P = 0.002, Student's t-test). The PSA-DT dynamics at progression had no effect on survival (P = 0.63, log-rank test). The pattern of progression after docetaxel-based chemotherapy is predominantly osseous in patient with bone metastases and mostly soft-tissue in those with soft-tissue disease. Progression after docetaxel-based chemotherapy in AIPC does not modify the PSA-DT before docetaxel. Evaluation of a larger population is needed to assess the clinical relevance of PSA dynamics after docetaxel therapy.

Nonneutropenic febrile episodes associated with docetaxel-based chemotherapy in patients with solid tumors.

Docetaxel is associated with severe lymphopenia and increased incidence of nonneutropenic infection. This study investigated the incidence of nonneutropenic infections and/or febrile episodes in patients with solid tumors receiving frontline docetaxel-based chemotherapy. Chemotherapy-naive patients with solid tumors treated with docetaxel-based chemotherapy were studied prospectively for the development of nonneutropenic infections. During a 2-year period, 680 cancer patients enrolled in 24 protocols received 2867 cycles of docetaxel-containing chemotherapy. Fifty-three patients (7.8%) developed nonneutropenic infections and/or febrile episodes. The most common of these were pulmonary infections (n = 25), Pneumocystis carinii interstitial pneumonias (n = 5), and candidal (n =11), herpetic (n =4), and cytomegaloviral (n =3) infections. Thirty-six patients (68%) had severe lymphopenia (< 900 cells per deciliter) and 49 (92%) had less than 400 CD4(+) cells per deciliter. Patients with a low CD4(+) cell count (</= 200 cells per deciliter) had a significantly higher probability to develop opportunistic than common infections (P = 0.002). The incidence of nonneutropenic infections and/or febrile episodes was significantly higher in patients treated with docetaxel/gemcitabine (18.3%; P = 0.0001) and docetaxel/CDDP (11.7%; P = 0.012) than in those treated with docetaxel alone (3.6%). Conversely, 175 patients who received 752 cycles of chemotherapy with paclitaxel-containing regimens and 410 patients who received 2174 cycles with nontaxane-based regimens developed 6 (3.4%; p=0.042) and 12 (3%; p=0.001) nonneutropenic infections, respectively. Less than 10% of the patients of the two latter groups were lymphopenic. The risk of nonneutropenic infection in patients receiving docetaxel-based chemotherapy was 2.38 and 2.8 times higher than in patients receiving paclitaxel and nontaxane-based chemotherapy, respectively. Patients treated with docetaxel-based chemotherapy are at increased risk of developing nonneutropenic infections. This may be related, at least partly, to severe postchemotherapy CD4(+) lymphopenia.

Colitis associated with docetaxel-based chemotherapy in patients with metastatic breast cancer

Docetaxel and vinorelbine as combined treatment for metastatic breast cancer can have the dose-limiting toxic effects of mucositis and neutropenic fever. We report unexpected ischaemic colitis in six patients associated with docetaxel-based therapy, three of whom were treated in a phase I study designed to establish the maximum tolerated dose of this combination with the prophylactic use of granulocyte-colony-stimulating factor. Between August, 1997, and December, 1998, 14 patients with metastatic breast cancer were treated with vinorelbine, docetaxel, and granulocyte-colony-stimulating factor in a phase I study. Three patients developed colitis similar to that seen in typhlitis. Three additional patients were identified during scheduled review of toxic effects in patients participating in clinical trials involving docetaxel. Three patients on combined vinorelbine and docetaxel developed colitis-like symptoms. Two patients died, one from necrotic bowel and the other from neutropenic fever and colitis. Two of the patients presented on day 7 and day 8 of chemotherapy, respectively, with neutropenic fever and abdominal pain; the third patient developed neutropenia without fever and abdominal pain on day 8. The other three patients were treated with docetaxel, docetaxel and pamidronate disodium, or docetaxel and cyclophosphamide. All three patients presented with abdominal pain on days 10, 5, and 4, respectively. One had non-neutropenic fever, another had neutropenic fever, and the third was afebrile and non-neutropenic at the time of presentation with abdominal pain. Three patients had blood in their diarrhoea, abdominal tenderness, or both. Computed tomography of the abdomen and pelvis showed features of colitis in three patients. This serious complication may result from the use of docetaxel and may be exacerbated by its combination with vinorelbine. Study of hospital-based patients treated with taxane-based chemotherapy is underway to find out the frequency of such complications.