Dose Intensity Of Docetaxel Research Articles

Impact of Relative Dose Intensity of Docetaxel, Cisplatin, and 5-Fluorouracil Neoadjuvant Chemotherapy on Survival of Esophageal Squamous Cell Cancer Patients

Introduction: This study aimed to clarify the impact of the average relative dose intensity (RDI) of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-NAC) for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: To identify the optimal RDI, recurrence-free survival (RFS) and cumulative incidence function (CIF) for recurrence were calculated in low and high RDI groups with any cut-off points. The optimal RDI was defined as the highest RDI administered with a significant increase in either RFS or CIF. The clinicopathological characteristics of the two groups divided by optimal RDI were investigated. The preoperative prognostic factors associated with RFS were confirmed by multivariable Cox proportional hazards model. Results: Among the 150 eligible patients treated with DCF-NAC from 2010 to 2020, 3-year RFS and CIF were 56.3% and 37.8% in 90 patients in the less than 80% RDI group (<80% RDI) and 73.3% and 26.7% in 60 patients in the more than or equal to 80% RDI group (≥80% RDI), respectively. The optimal cut-off RDI was identified as 80%. The <80% RDI group included older individuals, a lower value of creatinine clearance, a higher Charlson Comorbidity Index, reduced RDI at first course, and grade 1–0 in the histopathological tumor response than the ≥80% RDI group. R0 resection and postoperative complication rates were equal in both groups. Cox proportional hazards model identified the response rate and RDI as predictors of RFS. Conclusion: An average RDI of more than or equal to 80% improved prognosis in patients receiving DCF-NAC for ESCC.

Impact of Dose Intensity on Pathologic Complete Response Rate in HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Docetaxel, Carboplatin, Trastuzumab and Pertuzumab (TCHP).

Neoadjuvant chemotherapy is the cornerstone treatment for locally advanced breast cancer. Balancing toxicity and efficacy are a common concern of patients treated with chemotherapy. The objective of this study was to determine the impact of dose intensity on pathologic complete response (pCR) at the time of surgery in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. A retrospective, single-center review was conducted on patients with HER2+ breast cancer who received neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) followed by definitive surgery. A total of 159 patients were included in the analysis; pCR was obtained in 66 patients (42%). There was no statistically significant difference between the mean dose intensity of each of the individual agents in TCHP and pCR rates. The mean overall dose intensity of docetaxel, carboplatin, trastuzumab and pertuzumab was 90.5%, 90.9%, 97.5%, and 93.9%, respectively. Although higher chemotherapy dose intensity (>85%) was associated with higher pCR rates, no statistically significant difference was found compared with chemotherapy dose intensity <85%. The TCHP regimen was difficult to tolerate; 104 patients (65%) required a dose reduction or dose delay during treatment due to toxicity. The TCHP regimen, which combines chemotherapy and HER2-directed therapy is effective at obtaining pCR in patients with locally advanced HER2+ breast cancer. These results suggest that the dose intensity of the individual agents did not have a significant impact on pCR rates. Given these findings, providers may be more comfortable allowing dose reductions for greater patient tolerability without sacrificing efficacy.

Phase II feasibility study of adjuvant chemotherapy with docetaxel/cisplatin/S-1 followed by S-1 for stage III gastric cancer

BackgroundThis study aimed to evaluate the feasibility, safety, and efficacy of postoperative adjuvant chemotherapy with docetaxel/cisplatin/S-1 (DCS) following S-1 therapy in patients with stage III gastric cancer after curative gastrectomy.MethodsPatients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Adjuvant chemotherapy was initiated within 8 weeks of gastrectomy. The first cycle of chemotherapy consisted of S-1 monotherapy (day 1–14), followed by a 7-day rest period. Cycles 2 and 3 consisted of the following: S-1 (day 1–14) administration, followed by a 14-day rest period, and an intravenous infusion of cisplatin and docetaxel on days 1 and 15. After two cycles, S-1 was administered for up to 1 year.ResultsThirty patients were enrolled between 2014 and 2017. Febrile neutropenia of grade 3 or higher was the most common hematological toxicity with 4 patients (13.3%). Other hematological toxicities of grade 3 or higher were as follows: neutropenia in 3 (10.0%), leukopenia in 3 (10.0%), and anemia in 2 (6.7%) patients. Most frequent non-hematological toxicity of grade 3 was anorexia (n = 4, 13.3%) and general fatigue (n = 3, 10.0%); no grade 4 non-hematological toxicities were observed. Twenty-five patients (83.3%) completed two cycles of DCS treatment and 18 (60.0%) completed subsequent S-1 treatment for 1 year. The relative dose intensity of docetaxel and cisplatin was 0.86 and that of S-1 was 0.88.ConclusionThe DCS regimen can be acceptable as an adjuvant chemotherapy and offers an effective postoperative treatment option for stage III gastric cancer patients.Trial registration numberUMIN000012785.Date of registry08/01/2014.

A management of neutropenia using granulocyte colony stimulating factor support for chemotherapy consisted of docetaxel, cisplatin and 5-fluorouracil in patients with oesophageal squamous cell carcinoma

An exploratory study was designed to evaluate the efficacy of granulocyte colony stimulating factor support for chemotherapy consisting of docetaxel, cisplatin and 5-fluorouracil chemotherapy in patients with oesophageal cancer. The inclusion criteria were as follows: (1) oesophageal squamous cell carcinoma, (2) a schedule to receive three courses of induction chemotherapy (docetaxel 75mg/m2 day 1, cisplatin 75mg/m2 day 1, 5-fluorouracil 750mg/m2 days 1-5, every 3weeks), (3) stage IB-III, (4) 20-75years old, (5) 0-1 performance status, (6) preserved organ functions and (7) written informed consent. The endpoints were to evaluate the efficacy of granulocyte colony stimulating factor support including secondary prophylactic usage for docetaxel, cisplatin and 5-fluorouracil chemotherapy. Patients who previously had 'febrile neutropenia', or 'Grade 3 or 4 infection accompanied by grade 3 or 4 neutropenia' prophylactically received granulocyte colony stimulating factor support from day 7. A total of 91 patients were included in the analysis. Granulocyte colony stimulating factor support was given to 81.3%. The incidence of grade 4 neutropenia and febrile neutropenia were 81.3 and 32.9%, respectively. The dose of anticancer agents was reduced in 48.4%. There were no treatment-related deaths. The relative dose intensity of docetaxel, cisplatin and 5-fluorouracil were 92.7±9.8%, 86.0±15.6% and 91.8±10.0%, respectively. In the secondary prophylactic granulocyte colony stimulating factor support group, the neutrophil count significantly increased between day 7 and day 13 as compared with the non-prophylactic granulocyte colony stimulating factor support group (P<0.05 for each day). Granulocyte colony stimulating factor support including secondary prophylactic usage may be feasible for maintaining the intensity of docetaxel, cisplatin and 5-fluorouracil chemotherapy in patients with oesophageal cancer.

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer.

Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis, we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS). All patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 and September 2017 were identified. The association between relative dose intensity (RDI) and OS was assessed using univariate and multivariable Cox model adjusting for age, Gleason score, burden of disease, visceral involvement, de novo metastases and baseline prostate-specific antigen (PSA). Eighty-one patients were included in the analysis. Only 35 patients (43%) were able to complete the planned treatment with a RDI of at least 90%. On a univariate analysis, higher RDI and number of cycles of docetaxel received were associated with longer OS. For every 10% decrease in RDI, the risk of death increased by 23% (HR 1.23, 95% CI 1.09-1.4, P = 0.001). For every increment of one cycle (and up to six), the risk of death decreased by 27% (HR 0.73, 95% CI 0.61-0.88, P = 0.001). On multivariate analysis, reduced RDI was the only predictor significantly associated with OS (HR 1.18, 95% CI 1.02-1.36, P = 0.026). Our study suggests that in mCSPC, reduced docetaxel RDI is associated with shorter survival. Unnecessary dose reductions, treatment delays and early discontinuation should be avoided. Granulocyte colony-stimulating factor may be considered to maintain standard DI.

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer.

e16501 Background: Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS). Methods: We have identified all the patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 - September 2017. For each patient we calculated the relative dose intensity (RDI) and assessed whether it’s associated with OS using univariate and multivariate cox-proportional hazards analysis. Results: Eighty-0ne patients were included in the analysis. Nineteen patients (23.5%) had their body surface area capped at 2 which resulted with de facto median dose reduction of 7% (IQR 6% - 9%). Ten patients had upfront dose reduction (usually due to significant co-morbidities) with a median dose reduction of 20% (IQR 19.25 – 20.75). Only 35 patients (43.2%) were able to complete the planned treatment with a RDI of at least 90%. After a median follow-up of 29.4 months, 32 patients (39.5%) died. The median OS was 43.9 months. On a univariate analysis RDI and number of cycles of docetaxel received were found to be statistically significant associated with OS. For every 10% decrease in RDI the risk of death increased by 23% (HR 1.23, 95% CI 1.09 – 1.4, P = 0.0011). For every incremental cycle (up to a total of 6) the risk of death decreased by 27% (HR 0.73, 95% CI 0.61- 0.88, P = 0.001). On multivariate analysis we included age, Gleason score, burden of disease, visceral involvement and baseline PSA. Reduced RDI remained the only significant variable associated with OS (HR 1.2, 95% CI 1.04 – 1.39, P = 0.0117). Conclusions: Reduced docetaxel DI administrated to mCSPC patients is associated with worse survival. Therefore unnecessary docetaxel dose reductions, treatments delays and early discontinuation should be avoided. Granulocyte-colony stimulating factor should be considered in order help maintain standard DI.

A randomized phase II study of pelareorep (REO) plus docetaxel vs. docetaxel alone in patients with metastatic castration resistant prostate cancer (mCRPC): Canadian Cancer Trials Group study IND 209.

5021 Background: Pelareorep (REO) is an oncolytic virus with in vitro and in vivo activity in many cancers, including prostate. It has in vitro synergism with microtubule targeted agents especially taxanes. We undertook a clinical trial to evaluate REO in mCRPC patients (pts) receiving docetaxel. Methods: In this randomized, open-label multicenter phase II study, pts received docetaxel 75mg/m2 on day 1 of a 21-day cycle in combination with REO given as 3x1010 TCID50 IV daily on days 1-5 (arm A), or alone (arm B). The primary endpoint was 12-week lack of disease progression (LPD) rate. Secondary endpoints included objective response rate; survival; circulating tumor cell (CTC) enumeration at 0, 6 and 12 weeks; PSA response rate and biomarkers. Results: Eighty-five pts were randomized. Median age was 69, ECOG performance status (PS) was 0/1/2 in 31%/66%/3% of pts. Bone/regional lymph node/liver metastases were present in 98%/24%/6% of pts. More pts in arm A had poor prognostic factors for survival at baseline (median prognostic index 1.44 vs. 1.29). The median number of cycles delivered for arms A/B was 7/9 (range 1-10 and 1-13). In arm A, 51%/68% of pts received ≥90% of planned dose intensity of docetaxel/REO respectively, vs. 76% of pts for docetaxel in arm B. Adverse events (AE) were as expected for docetaxel therapy but more prevalent in arm A (grade 3 or higher all AEs 80 vs. 74%). A higher rate of grade 4 febrile neutropenia was noted in arm A (7 vs. 0%) but may represent virus related fevers. The 12-week LPD rate was 61% and 52.4% in A/B respectively (p = 0.51). OS was worse in arm A vs. B (HR 1.95; 95% CI 0.94-4.06; p = 0.07 after adjusting for age, PS and baseline prognostic score). There was no difference between arms in CTC favourable status at any timepoint. No survival benefit of REO with D was found in any subset from the biomarker analysis. Conclusions: While the combination of REO with D for patients with mCRPC was tolerable and LPD rate was comparable in both arms, docetaxel dose intensity and survival were inferior and so this combination, as tested, does not merit further study. Clinical trial information: NCT01619813.

Safety Analysis of Adjuvant Chemotherapy with Docetaxel Administered with or without Anthracyclines to Early Stage Breast Cancer Patients: Combined Results from the Asia- Pacific Breast Initiatives I and II.

The Asia-Pacific Breast Initiatives (APBI) I and II registries were established to collect safety data for patients with early stage breast cancer receiving adjuvant docetaxel-based regimens in the Asia-Pacific region. Data from the two registries were combined to perform a safety analysis. Participants in the registry were women with early stage operable breast cancer with an intermediate or high risk of recurrence. These women received adjuvant chemotherapy that included docetaxel between 2006 and 2011. Adverse events (AEs) were recorded and analyzed. Data were collected from 3,224 patients from 13 countries. The mean dose intensity of docetaxel was 24.1, 22.7, 25.1 mg/m2/week among patients receiving docetaxel-based monotherapy, combination therapy and sequential therapy, respectively. Granulocyte colony-stimulating factor (G-CSF) was given with docetaxel to 41.8% of women and 20.6% of women receiving prophylactic antibiotics. Adverse events were reported in 86% of patients (anthracycline-containing regimens vs. non-anthracycline regimens; 87% vs. 80%). The most common adverse events were alopecia, nausea, neutropenia, vomiting, and myalgia. Adverse events NCI CTCAE ≥Grade 3 were reported in 45.4% of patients. Serious adverse events were reported in 13% of patients, of which 2.5% led to study discontinuation. Forty-six deaths (1.4%) were reported, with no significant difference between regimens. The safety parameters of adjuvant docetaxel therapy used to treat sequential Asian women were comparable to those reported in clinical trials evaluating the role of adjuvant docetaxel. No unusual adverse events linked to Asia-Pacific region patients were observed.

Docetaxel-based adjuvant therapy for breast cancer patients in Asia-Pacific region: Results from 5 years follow-up on Asia-Pacific Breast Initiative-I.

To acquire patient characteristics, safety, relapse and survival outcomes of early-stage breast cancer patients receiving docetaxel (Taxotere(R))-based regimen in adjuvant setting from the Asia-Pacific region. This was an open-label, international, longitudinal, multicenter, observational, prospective cohort of consecutive early breast cancer (EBC) patients with a high risk of recurrence being treated with various docetaxel-containing anthracycline and non-anthracycline adjuvant regimens during 2006-2013. In this study, 1542 patients were enrolled. Anthracycline-containing regimens were administered in 92% of patients, while 8% of patients received non-anthracycline-containing docetaxel-based regimens. The mean dose intensity of docetaxel was 25.8, 22.4 and 25.4 mg/m(2) /week among patients receiving docetaxel-based monotherapy, combination and sequential therapy, respectively. Adverse events were reported in 94.9% of patients (anthracycline vs non-anthracycline regimen; 95.1% vs 93.5%). Serious adverse events were reported in 12.6% of patients (12.4% vs 14.6%). Grade 4 neutropenia was reported in 25.2% of patients (24.7% vs 30.9%) and febrile neutropenia in 1.9% of patients (2% vs 0.8%). Only 7% of patients had a relapse or a second primary malignancy. At 5-year follow-up, there were 127 (8.3%) deaths (8.4% vs 6.5%). The Asia-Pacific Breast Initiative-I registry highlights the important patient and treatment characteristics of EBC patients treated with adjuvant docetaxel chemotherapy from the Asia-Pacific region that will help physicians to understand the impact of different docetaxel treatments on the clinical outcomes in this population.

Phase I/II docetaxel, oxaliplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.

162 Background: The results of recent studies with duo- or triple regimen for the advanced gastric cancer are still not satisfactory and the optimal doses of combinations with taxanes, fluorouracil and platinum analogues were not determined yet. The aim of this study is to determine the optimal dose of docetaxel and oxaliplatin in combination with 5-fluorouracil(FU) [DOF], with the efficacy and toxicity in patients (pts) with advanced gastric cancer. Methods: The pts with unresectable, metastatic, or relapsed gastric cancer were enrolled for a phase I/II study. The dose of docetaxel and oxliplatin was escalated from 50 mg/m2 and 80 mg/m2 day 1, respectively by traditional 3+3 design, and 5-FU was fixed at 850 mg/m2/day 24 hour continuous infusion day 1-4, all every 3 weeks. All pts had measurable disease and were assessable for toxicity. Results: A total of 50 pts including 12 patients from phase I study were enrolled. The recommended phase II dose of docetaxel and oxaliplatin were 60mg/m2 and 100mg/m2 on day 1 (cohort 2), respectively. A total of 335 cycles of chemotherapy was administrated (median: 6, range 1–24) and the dose intensity of docetaxel, oxaliplatin, and 5-FU were 96.3%, 96.2% and 98.5%, respectively. Twenty two (44.0%) of 50 patients showed partial response, 22 (44.0%) stable disease, and 1 (2.0%) complete response. The overall response rate was 46.0% (95% confidence interval [CI]: 32.2–60.0%) and the disease control rate 90.0% (95% CI: 81.7–98.3%). The median progression free survival was 6.5 months (95% CI, 3.3–9.8) and the overall survival 10.7 month (95% CI, 7.0–14.3). Grade 3/4 neutropenia and thrombocytopenia occurred in 81 (24.1%) and 3 cycles (0.9%), respectively [27 (56%) and 3 (6%) in 50 pts, respectively]. Grade 3/4 stomatitis, diarrhea and neuropathy occurred in 2 (0.6%), 6 (1.8%) and 6 cycles (5.7%), respectively. Conclusions: The recommended phase II dose of docetaxel and oxaliplatin was 60mg/m2 and 100mg/m2, respectively. This DOF combination chemotherapy has no better efficacy than reference regimen. The toxicities were substantial in some pts, but generally manageable.

Adjuvant FEC-D: Dose intensity and survival—What is optimal?

e12001 Background: Dose intensity has long been felt to be important in achieving maximal benefit (disease free and overall survival) from chemotherapy regimes in the adjuvant breast cancer setting. However, increasing dose intensity increases toxicity. Although many studies report dose intensity, few report the longer-term relationship between dose intensity achieved and survival benefit. Methods: A retrospective review was performed on 101 consecutive patients treated with FEC-D (FE100C x 3 docetaxel 100 mg/m2x 3) between Jan 2006 and Dec 2007 and the relative dose intensity for docetaxel calculated. The relationship between dose intensity and outcome was explored and related to outcomes in the PACS-01 trial (primary endpoint DFS, secondary endpoint OS, n=1,999). Results: Median age was 54 yrs (range 30-70). 43% ER positive, 52% HER2 positive (see Table). Extraction of patients receiving <85% docetaxel dose intensity (22 patients) showed DFS of 77.3%, OS 81.8% (18 patients alive), and with 41 patients r...

OP0013 An interim safety analysis of adjuvant chemotherapy with docetaxel, administered with or without an anthracycline-based regimen, in early-stage breast cancer: A clinical observational study (Asia Pacific Breast Initiatives I and II)

Background The Asia Pacific Breast Initiatives (APBI) I and II were set up to capture data for patients with early-stage breast cancer receiving docetaxel-based regimens in adjuvant chemotherapy. Data from the two registries were combined for an interim safety analysis. Methods We analysed pooled data from the APBI registries, which included patients newly diagnosed with early-stage operable breast cancer with a high risk of recurrence who were receiving a range of docetaxel-based adjuvant chemotherapy regiments during 2006–2011, from 13 countries. Adverse events (AEs), serious adverse events (SAEs), and deaths were categorised and analysed to assess the comparative safety of the anthracycline and non-anthracycline groups. Findings The safety analysis was done in 3224 datasets. The therapy-wise classification of patients is shown in the table. The mean dose intensity of docetaxel was 24.1, 22.7, and 25.1 mg/m 2 per week in patients receiving docetaxel-based monotherapy, combination, and sequential therapy, respectively. Of the chemotherapy support drugs administered, 35.60% and 19.67% of the overall population received growth factor support (granulocyte colony-stimulating factor, G-CSF) and antibiotics, respectively. Exploratory analysis revealed that the proportion of patients receiving G-CSF was numerically higher in the combination arm (62.5%) compared with the arm receiving sequential therapy (25.9%) with docetaxel; antibiotics were given to 20.5% and 21.5% of patients in these categories, respectively. AEs of grade 3 or worse were reported in 45.4% of patients. AEs related to chemotherapy were reported in 45.4% and 37.6% of patients receiving anthracycline and non-anthracycline chemotherapy, respectively. The most common AEs in the two groups were alopecia (57.8% of patients on anthracyclines versus 49.3% of those on non-anthracycline regimens), nausea (58.2% versus 30.2%), decreased neutrophils (45.3% versus 29.4%), vomiting (43.3% versus 14.2%), and diarrhoea (24.1% versus 23.5%). SAEs were reported in 13% of the overall population. Overall, 46 deaths (1.4%) were reported, of which 41 were in the anthracycline group and five were in the non-anthracycline group. Interpretation The combined analysis of results shows that the safety profiles of anthracycline-based and non anthracycline-based chemotherapy regimens are comparable. Concurrent use of docetaxel appeared to require more G-CSF support than sequential therapy.

Feasibility Study of Docetaxel and Cyclophosphamide Six- Cycle Therapy as Adjuvant Chemotherapy for Japanese Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients

We compared treatment completion rates and safety of docetaxel and cyclophosphamide six- cycle therapy (TC6) with docetaxel followed by 5FU, epirubicin and cyclophosphamide (T-FEC) therapy in Japanese patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer. We administered TC6 q3w or T-FEC q3w to HER2-negative breast cancer patients. The primary endpoint of this trial was toxicity. As second endpoints, the treatment completion rate and relative dose intensity were evaluated. The TC6 and T-FEC group consisted of 22 and 21 patients, respectively. Concerning hematological toxicity, grade 3 or higher adverse reactions included neutropenia and febrile neutropenia. As non-hematological adverse events, exanthema and peripheral neuropathy were frequently reported in the TC6 group, whereas more patients of the T-FEC group reported nausea and vomiting. In TC6, the treatment completion rate was 86.4% and the relative dose intensity of docetaxel was 93.2%. In T-FEC, the values were 95.2% and 98.9%, respectively. These results suggest that TC6 is tolerable in Japanese, and that this regimen can also be performed in outpatient clinics. However, with the TC6 regimen, the compliance was slightly lower than with the T-FEC regimen, and supportive therapy needs to be managed appropriately.

Feasibility and safety of dose-dense docetaxel after conventional epirubicin and cyclophosphamide as adjuvant treatment for early breast cancer patients

BackgroundAlthough dose-dense chemotherapy may reduce breast cancer recurrence and death, phase II studies show that dose-dense docetaxel is poorly tolerated following administration of dose-dense anthracycline-based chemotherapy mainly because of cutaneous toxicity. Material and methodsThis pilot study was designed to explore feasibility and safety of dose-dense docetaxel after conventional anthracycline-based therapy.Treatment consisted of sequential administration of 4 cycles of 3-weekly epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2), followed by 4 cycles of bi-weekly docetaxel with pelfilgrastim on day 2 of each docetaxel cycle. Two docetaxel dose levels were planned: 75 mg/m2 (D75) and 100 mg/m2 (D100). Patients could only be assigned to the higher docetaxel dose if no early treatment discontinuations due to toxicity were seen, and a median relative dose intensity of docetaxel >90% among the first 5 evaluable patients was achieved. ResultsFifty three patients received 4 cycles of epirubicin/cyclophosphamide (EC). Six patients withdrew from study before commencing docetaxel: four for toxicity, and two who declined further study participation.Eight patients, 2 in the first dose level and 6 in the second dose level, stopped treatment for toxicity after the first cycle of docetaxel and before densification. Therefore these events were not considered early treatment discontinuations. No patients required dose interruption after the second docetaxel administration. Overall 5 patients in the first dose level and 34 patients in the second dose level received 4 cycles of accelerated (dose-dense) docetaxel. No grade 3 or grade 4 toxicities occurred at the first dose level. No grade 4 toxicities occurred at the second dose level, while grade 3 toxicities occurring in >2 patients were myalgia and bone pain (5 and 8 patients respectively, 13% and 20%) and skin-nail toxicity (7 patients, 21%). No dose-reductions or significant treatment delays were required, translating to median relative dose intensity of 100% for docetaxel 75 mg/m2, and 99% for 100 mg/m2. ConclusionsAdministration of docetaxel 100 mg/m2 bi-weekly after conventional EC is feasible in selected early breast cancer patients. Lack of prior exposure to dose-dense anthracycline, as well as the use of stringent criteria implemented in the treatment protocol, might explain the improved safety profile and high treatment compliance observed in this study.

Clinical outcomes by relative docetaxel dose and dose intensity as chemotherapy for Japanese patients with castration-resistant prostate cancer: a retrospective multi-institutional collaborative study

The aim of this study was to retrospectively investigate clinical outcomes by relative dose and dose intensity of docetaxel (DOC) as chemotherapy for Japanese patients with castration-resistant prostate cancer (CRPC). A total of 145 CRPC patients who received more than 4 courses of DOC chemotherapy at 14 hospitals between 2005 and 2011 were enrolled. Patients were divided into two groups--those receiving a higher or lower dose (mg/m(2)) or dose intensity (mg/m(2)/week). Differences between the groups regarding treatment outcomes and adverse events (AEs) were determined. Additionally, prognostic factors predictive of cancer-specific survival (CSS) in these patients were identified by both univariate and multivariate analysis. The total patient group underwent a mean of 11.2 ± 7.4 DOC cycles, and the mean CSS after therapy was 15.6 ± 10.1 months. The higher-dose group had a better prostate-specific antigen (PSA) response than the lower-dose group. However, there was no significant difference between the groups in prognosis after DOC chemotherapy. Leukopenia and neutropenia were observed more frequently in the higher-dose group. Serum biomarkers (including PSA, lactate dehydrogenase and alkaline phosphatase), hemoglobin levels and presence of pain at initiation of chemotherapy, as well as the PSA nadir level on first-line hormone therapy, all were significant predictors of CSS. In the Japanese population, relatively low-dose DOC chemotherapy had no deleterious effect on the CSS of CRPC patients, and a lower incidence of AEs occurred, in spite of a diminished PSA response compared with those receiving a higher dose.

The safety and tolerability of FE100C-D chemotherapy in a non-trial population of node positive breast cancer compared to PACS-01 trial group; Salmaniya Medical Complex experience

Introduction: In our institution, adjuvant taxanes are currently offered to fit node-positive breast cancer patients who are either Her2 positive (any ER/PR) or triple negative (ER/PR/Her2 negative). The FE 100 C-D (FE100C × 3 → docetaxel 100 mg/m 2 × 3) regime, based on the PACS 01 trial1 is used. Materials and Methods: We retrospectively audited our experience with FE 100 C-D at Salmaniya Medical Complex. Over a 2-year-period, 100 patients commenced adjuvant FE100C-D chemotherapy. Data was matched with the FE 100 C-D arm of the PACS 01 trial. Results: Median age was 54 years. Twenty-six patients (26%) had ≥1 episode of febrile neutropenia (FN), including one fatal episode; 29% patients required treatment interruption ≥1 week; 30% patients had dose reductions; and 30% patients received < 90% dose intensity of docetaxel. Conclusion: The FN rate was substantially higher and docetaxel dose intensity substantially lower in our unselected sample of patients than in the trial population, this real-life data demonstrates the problems of applying clinical trial data to the more generalised patient population. Meanwhile, the routine use of prophylactic G-CSF support with this protocol is warranted.

Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer

Background:Locally advanced oesophageal cancer (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this phase I trial was to assess the maximum tolerated dose (MTD) of a novel weekly docetaxel and cisplatin regimen concurrent with radical radiotherapy.Methods:Patients with unresectable, non-metastatic LAEC were eligible. Treatment comprised docetaxel 15–30 mg m−2 per week and cisplatin 15–30 mg m−2 per week in six planned dose levels (DLs) in 3–6 patient cohorts with 50 Gy radiotherapy in 25 fractions. Maximum tolerated dose was based on defined dose-limiting toxicities (DLTs) during therapy and 2 weeks post therapy.Results:A total of 24 patients were enrolled. There were two DLTs: grade 3 fever in DL1 (docetaxel 15 mg m−2, cisplatin 15 mg m−2) and grade 3 nausea in DL2 (20 mg m−2, 15 mg m−2). These DLs were each expanded to six patients without further DLTs. The most common acute toxicity was grade 3 radiation oesophagitis (37.5%). There were no grade 4 toxicities, and haematologic toxicity was minimal. Cisplatin and docetaxel dose intensity was 100% at the highest dose level (DL6). A MTD was not reached in this trial. Tumour overall response rate was 50% (33% complete, 17% partial).Conclusion:Cisplatin and docetaxel each 30 mg m−2 per week concurrent with 50 Gy radiotherapy is recommended for use in phase II clinical trials in oesophageal cancer.

Are patients in clinical trials representative of the general population? Dose intensity and toxicities associated with FE 100C-D chemotherapy in a non-trial population of node positive breast cancer patients compared with PACS-01 trial group

Purpose In our institution, adjuvant taxanes are currently offered to fit, node positive breast cancer patients who are either Her2 positive (any ER/PR) or triple negative (ER/PR/Her2 negative). The FE 100C-D (FE 100C × 3 → docetaxel 100 mg/m 2 × 3) regime, based on the PACS 01 trial [Roche H, Fumoleau P, Spielmann M, et al. Sequential Adjuvant Epirubicin-Based and Docetaxel Chemotherapy for node positive Breast Cancer Patients: The FNCLCC PACS 01 Trial. J Clin Oncol 2006;24:5664-5671] is used. We retrospectively audited our experience with FE 100C-D at The Beatson West of Scotland Cancer Centre and one representative district general hospital (DGH), Falkirk and District Royal Infirmary (FDRI). Patients and methods Over a two year period, 101 patients commenced adjuvant FE 100C-D chemotherapy. Data was matched with the FE 100C-D arm of the PACS 01 trial. Results Median age was 54 years. Twenty-six patients (26%) had ⩾1 episode of febrile neutropaenia (FN), including one fatal episode. Twenty-nine percent of patients required treatment interruption ⩾1 week. Thirty percent of patients had dose reductions. Thirty percent of patients received <90% dose intensity of docetaxel. Conclusion The FN rate was substantially higher and docetaxel dose intensity substantially lower in our unselected sample of patients than in the reference study. 1 This ‘real-life’ data illustrates the problems of applying clinical trial data to the more generalised patient population.

Sequential taxane and anthracycline-containing neoadjuvant regimens: The sequential order impact

BackgroundOne can consider as a standard neoadjuvant treatment for breast cancer, the sequence of 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel. Based on the belief that the sequence order between anthracycline and taxane might be of interest, this study assessed the impact of the sequence order. MethodsOne hundred and twenty three patients with breast cancer were treated with neoadjuvant chemotherapy in 5 oncologic centers between 2003 and 2007. This study compared 65 patients treated with 4 cycles of docetaxel followed by 4 cycles of anthracycline-based chemotherapy (cohort T), versus another cohort of 58 patients treated with 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel (cohort A). ResultsThe overall dose intensity of docetaxel and clinical complete responses were significantly higher in cohort T. No statistically significant differences were observed in terms of conservative surgeries or histological responses. The sequence of chemotherapy did not significantly influence other treatment-related toxicities. Mild neurotoxicity was higher in patients treated in cohort T. Anemias (≥Grade 1) were higher in cohort A (52% versus 81%; p = 0.0008). ConclusionThe present study failed to identify an impact of the sequence of taxane administration on the efficacy. Nevertheless, starting neoadjuvant chemotherapy by taxane reduces the occurrence of anemia. These findings might allow a selection of the sequence order based on the toxicity profile.

A Dose Escalation Trial of Biweekly Docetaxel and Gemcitabine with Filgrastim or Pegfilgrastim for the Treatment of Patients with Advanced Solid Tumors

Background/Aims: A single-institution phase I trial to determine the feasibility of using filgrastim or pegfilgrastim to increase the dose intensity of biweekly docetaxel and gemcitabine. Methods: Patients with metastatic solid tumors received gemcitabine 3,000 mg/m² and increasing doses of docetaxel (55 mg/m² in 10 mg/m² increments) every 14 days with filgrastim or pegfilgrastim. Results: 35 patients enrolled, median 2 prior therapies, 158 cycles of therapy. There was 1 dose-limiting toxicity (DLT) (sepsis) at docetaxel 55 mg/m², 1 DLT (sepsis/diarrhea) at docetaxel 65 mg/m², and no DLT at docetaxel 75 mg/m². At docetaxel 85 mg/m², 2/4 patients had DLT (fatigue/dyspnea, diarrhea). The maximum tolerated dose (MTD) of docetaxel was 75 mg/m². 1/12 patients treated at MTD experienced DLT (sepsis/dyspnea). The initial 25 patients received filgrastim (average 7 doses/cycle), the last 10 received pegfilgrastim. Conclusions: The MTD for docetaxel was 75 mg/m² with gemcitabine 3,000 mg/m² given every 14 days with filgrastim or pegfilgrastim. This regimen was well tolerated with signs of clinical activity. We found no significant differences in toxicities or effectiveness between daily filgrastim and pegfilgrastim given 13 days before the next chemotherapy. The use of granulocyte growth factors allowed increased dose intensity of docetaxel and gemcitabine. This regimen warrants further study in chemotherapy-naïve patients and patients with earlier stages.