3-weekly Docetaxel Research Articles

IS3-6 - Multicenter Randomized Phase II Study of Weekly Docetaxel Alone Versus Weekly Docetaxel Plus Oxaliplatin as a Second-Line Chemotherapy in Patients with Advanced Gastric Cancer: Preliminary Response and Safety Results

ABSTRACT Background Gastric cancer is a frequent malignancy with worldwide estimated incidence of 990'000 cases, representing 7.8% of all cancers in 2008. There are limited data suggesting a benefit for doublet second-line chemotherapy in advanced gastric cancer. Methods The eligibility criteria were patients 1) with prior exposure to cisplatin based chemotherapy and advanced or recurrent stomach cancer 2) with pathologically proven gastric adenocarcinoma, 3) with an ECOG performance status 0 to 2, 4) with measurable lesions. Each treatment cycle was consisted of docetaxel 36 mg/m2 in docetaxel mono therapy group and docetaxel 36 mg/m2, oxaliplatin 80 mg/m2 in docetaxel/oxaliplatin doublet therapy group on days 1, 8. The primary end point of this study was response rate, and secondary end points included toxicity, progression free and overall survival. Results Fifty two patients were enrolled; median age was 63 years; male (n = 42) and female (n = 10); docetaxel mono therapy (n = 27) and docetaxel/oxalliplatin doublet therapy (n = 25). The median number of cycles administered was 2.5 (range,1-9). Fourty eight patients were assessable for efficacy. Four partial responses, 7 stable diseases in mono therapy group (RR; 4/27, 14.8%) and 1 complete remission, 4 partial responses, 13 stable diseases in double therapy group (RR; 5/25, 20.0%) were confirmed (P = 0.198). Median progression free survival was 1.97 months in the mono therapy group and 4.93 months in doublet therapy group (P = 0.007). Median overall survival was 11.57 months in the mono therapy group and 8.13 months in doublet therapy group (P = 0.650). Grade 3 or 4 adverse events were reported in 11 of 52 patients; G3 pain were in 2 patients and G3 pneumonia was in 1 patient in mono group, G3/4 neutropenia were 5 patients in the combination group, G3 nausea, vomiting, general weakness was 1 patient each group in combination group. Conclusions Weekly docetaxel/oxaliplatin doublet therapy showed superior progression free survival to monotherapy group as second line therapy in cisplatin pretreated advanced gastric cancer patients.

908P - Prognostic Value of Free Testosterone (FT) Levels During Salvage Chemotherapy with Carboplatin Plus Weekly Docetaxel in Metastatic Castration- and Docetaxel-Resistant Prostate Cancer (MDRPC)

ABSTRACT Background Recent data suggest that carboplatin plus weekly docetaxel (DC) is an effective salvage therapy in DRPC. Carboplatin, docetaxel and steroids all interfere with testosterone biosynthesis and/or metabolism. In this study the impact of DC treatment on testosterone serum levels was analyzed. Methods Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 71 consecutive DRPC pts were treated with at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. FT was measured before (n = 44) and during carboplatin/docetaxel chemotherapy (n = 38). Results Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 34/71 (47.9%) patients. At the time of the current analysis the median follow-up time was 14.5 months and 47/71 patients had died. Median progression-free survival (PFS) for all patients was 6.9 months (CI 95% 4.3, 13.6) and median overall survival (OS) was 18.0 months (CI 95% 10.4, 25.6). Median FT serum levels were 3.0 pmol/L before (n = 43) and below the RIA detection limit of Conclusion These data demonstrate for the first time that testosterone is an important prognostic factor for PFS and OS in mDRPC patients receiving chemotherapy. Disclosure C.W.M. Reuter: Minor consulting fees from Sanofi Aventis, Amgen, V. Grunwald: Consulting fees from Novartis, All other authors have declared no conflicts of interest.

Rational indication for docetaxel rechallenge in metastatic castration‐resistant prostate cancer

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Docetaxel rechallenge has shown preserved anti-tumour activity and has therefore been proposed as an option for further treatment in patients with metastatic castration-resistant prostate cancer, who have shown a good response to first-line chemotherapy with docetaxel. The present study provides evidence of docetaxel activity in patients who were treated with full-dose (75 mg/m(2) ) 3-weekly docetaxel at first-line chemotherapy and rechallenge. It shows that PSA response to first-line chemotherapy may provide a rational indication for docetaxel rechallenge. • To determine whether prostate-specific antigen (PSA) response at first-line chemotherapy with docetaxel correlates with PSA response and survival at docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC). • We retrospectively evaluated the oncological outcomes of patients with mCRPC, who were treated with full-dose (75 mg/m(2) ), 3-weekly docetaxel plus prednisone/prednisolone at first-line chemotherapy and rechallenge, between 1999 and 2011, at our institution. • The endpoints were PSA-progression-free survival (PSA-PFS) and overall survival (OS) at docetaxel rechallenge. • Statistical analyses included Kaplan-Meier curves and log-rank tests to evaluate the effect of PSA response at first-line chemotherapy on PSA-PFS and OS at rechallenge. • Fourty-four patients were included in the analysis. • At a median (range) follow-up of 26.4 (9.8-89.8) months after the first administration of docetaxel, 24 (55%) patients had died. At first-line chemotherapy, 36 (82%) patients achieved a reduction in PSA level of ≥50%. At rechallenge, 10 (28%) patients responded with a reduction of ≥50% for a second time. • The median (95% confidence interval [CI]) PSA-PFS was 5.9 (95% CI 3.5-6.8) months and the median OS was 21.8 (95% CI 19.9-23.7) months at docetaxel rechallenge. • Of the PSA response variables evaluated, only a PSA level reduction of ≥50% at first-line chemotherapy correlated significantly with prolonged PSA-PFS (5.8 vs. 4.5 months; P= 0.01) and OS (22.1 vs. 7.2 months; P= 0.03) at rechallenge. • In the present single-institution study, a reduction in PSA level of ≥50% at first-line chemotherapy with docetaxel correlated with superior PSA-PFS and OS in the rechallenge setting and might, therefore, present a rational indication for docetaxel rechallenge.

Docetaxel

Docetaxel (Taxotere®) is a well established anti-mitotic chemotherapy agent. Among other therapeutic indications, docetaxel plus prednisone is indicated for first-line chemotherapy in patients with castration-resistant prostate cancer (CRPC). Docetaxel every 3 weeks plus continuous prednisone has been standard first-line chemotherapy in CRPC since demonstrating improved survival compared with the previous standard regimen, mitoxantrone plus prednisone, in the phase III TAX 327 trial in 2004. Since that time, docetaxel has been combined with various agents that demonstrated additive or synergistic activity in preclinical studies in an effort to further improve outcomes, but to date, overall survival has not been extended compared with docetaxel plus prednisone. However, several promising agents are emerging with a potential role in docetaxel-based combinations based on efficacy and manageable toxicity, including bevacizumab, dasatinib and atrasentan. In the TAX 327 trial, neutropenia was relatively common in the group receiving 3-weekly docetaxel plus prednisone, but infection was rare. The tolerability of a weekly docetaxel regimen also administered in this trial was not significantly different to that of the 3-weekly regimen, except for a lower incidence of grade 3 or 4 neutropenia. However, weekly or 2-weekly docetaxel administration schedules may have a place in very elderly or frail patients in order to improve tolerability compared with the 3-weekly regimen. In conclusion, docetaxel every 3 weeks plus prednisone remains the optimum first-line chemotherapy for most patients with advanced CRPC until such time that ongoing research with docetaxel and emerging therapeutic agents can demonstrate improved survival.

MGCD265, a multitargeted oral tyrosine kinase receptor inhibitor of Met and VEGFR, in combination with docetaxel.

e13604 Background: MGCD265 is a multi-target oral tyrosine kinase receptor inhibitor that targets Met, VEGFRs 1, 2, 3, Tie and Ron. The maximum tolerated dose (MTD) of MGCD265 in combination with docetaxel was initially determined using micronized tablets. MGCD265 formulation was improved and the MTD of MGCD265 in combination with docetaxel using the updated formulation was re-evaluated. Methods: Patients (pts) with metastatic or advanced solid tumors were enrolled in this Phase I, open-label, dose-escalating study to assess safety, pharmacodynamics (PD) and pharmacokinetics (PK) as well as anti-tumor activity of the combination. MGCD265 was administered every day over a 3-week cycle and docetaxel (50 then 75 mg/m2) was given intravenously once every 3 weeks (q3w). Results: As of January 11, 2012, 34 pts were enrolled (M/F: 19/15; ECOG 0/1: 19/15; median age: 64 years old). The MTD of the combination was initially defined as MGCD265 (72 mg/m2 BID)+docetaxel (75 mg/m2 q3w) based on the occurrence of dose limiting toxicities (DLTs) in 2 pts who were treated with MGCD265 at 96 mg/m2 BID (fatigue in 1 pt and diarrhea & lipase elevation in the other pt). The updated formulation of MGCD265 was introduced at 48 mg/m2 BID (n=3) with dose escalation to 72 mg/m2 BID (n=3) and 96 mg/m2 (n=4) with no observed DLTs, though the exposure of the two formulations were generally comparable. Overall, objective partial responses (per RECIST 1.1) were observed in 2/9 pts with NSCLC, 1/3 pts with prostate cancer and 1/1 pt with endometrial cancer. Stable disease for 6 cycles or more was observed in 6 pts. Treatment-related ≥ grade 3 toxicity reported in ≥ 2 pts were neutropenia, leukopenia, diarrhea and elevated lipase. The PD profile indicated an increase in the plasma level of VEGF and a decrease in plasma level of HGF at Cycle 1 Day 8 compared to baseline in some patients. Conclusions: MGCD265 was found to be well tolerated using the updated formulation in combination with full-dose docetaxel. Anti-cancer activity, supporting Phase II development of the combination, was observed.

Gefitinib in Combination with Weekly Docetaxel in Patients with Metastatic Breast Cancer Caused Unexpected Toxicity: Results from a Randomized Phase II Clinical Trial

In patients with metastatic breast cancer, taxane treatment demonstrates activity but is not curative. Targeted treatment modalities are therefore necessary in order to improve outcomes in this group. A randomized placebo-controlled phase II trial was initiated to evaluate effect and toxicity of gefitinib (250 mg QD) and docetaxel 35 mg/m2 (six of seven weeks) (NCT 00319618). The inclusion of 66 patients was planned. The study was closed due to treatment-related toxicity. Of the 18 included patients, seven (of which three received gefitinib) were withdrawn from the study due to toxicity. Of the nine patients receiving gefitinib and chemotherapy, one achieved a partial response and four stable disease. In the chemotherapy of nine patients, four had a partial response and four stable disease. The breast cancer patients in this study were genotyped using a panel of 14 single-nucleotide polymorphisms (SNPs), previously found associated with docetaxel clearance in a cohort of lung cancer patients. We were unable to identify genes related to toxicity in this study. Nevertheless, toxicity was aggravated by the addition of the tyrosine kinase inhibitor. In conclusion, despite adequately tolerated as monotherapy, combination regimens should be carefully considered for overlapping adverse events in order to avoid increased treatment-related toxicity.

Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castration-resistant prostate cancer: Implications for prior therapy in clinical trials

ObjectivesAbiraterone acetate (AA) is a CYP17 inhibitor of androgen synthesis approved for use following docetaxel for metastatic castration-resistant prostate cancer (mCRPC); evaluation in the pre-docetaxel setting is ongoing. Given that the reported efficacy of AA is lower following docetaxel vs. pre-docetaxel, the potential exists for cross resistance given docetaxel's partly androgen receptor targeting activity. The efficacy of docetaxel following ketoconazole (KC), a weaker and nonspecific inhibitor of CYP17, may provide some insights into this potential interaction. We retrospectively evaluated the efficacy of every 3-week docetaxel with prednisone (DP) in mCRPC previously exposed to KC compared to KC-naive patients. Materials and methodsA randomized phase II trial of men with mCRPC treated with DP + AT-101 (bcl-2 inhibitor) vs. DP plus placebo was analyzed. Both arms were combined for analysis as no significant differences were seen. Overall survival (OS), progression-free survival (PFS), objective response (ORR), pain, and prostate-specific antigen (PSA) response rates were estimated with and without prior KC. Cox proportional hazards regression models were used to estimate the effect of covariates on OS. ResultsOf 220 evaluable men, 40 (18.2%) received prior KC. The median OS with DP-based therapy of KC-naive patients (18.3 months, 95% CI: 15.0, 24.5) and post-KC patients (17.0 months, 95% CI: 9.9, 20.4) was not statistically different (P = 0.20). After controlling for prognostic classifications, analyses demonstrated consistent trends for worsening of OS after KC, with (hazard ratios (HRs) 1.33–1.46. Similar unfavorable trends were observed for ORR, PSA declines, and PFS. ConclusionsIn this hypothesis-generating analysis, patients treated with docetaxel-based chemotherapy following prior KC had numerically and consistently worse outcomes than patients not exposed to prior KC. Although the estimated differences did not attain statistical significance, evaluation of outcomes with docetaxel in particular, and all classes of novel and emerging agents following AA, is of clinical importance, given its more potent androgen synthesis inhibition compared with KC. Drug development should take into account the potential impact of previous therapy.

Short post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia

The patient impact of chemotherapy-induced alopecia (CIA) is high. Scalp cooling is applied to reduce CIA. The potential optimum post-infusion cooling times (PICTs) are currently unknown. Scalp cooling was applied in 53 patients receiving docetaxel chemotherapy with 90-min PICT (observational part). Also 15 non-scalp-cooled patients were included. If hair preservation was observed in >80 % of the patients, randomisation between 45 and 90-min PICT was planned. Patients reported tolerance of scalp cooling and use of head covering. Observational study: 81 % of scalp-cooled patients did not require head covering versus 27 % of non-scalp-cooled patients. Randomised study: 79 % of 38 patients with 90-min PICT did not need head covering versus 95 % of 38 patients with 45-min PICT (p = 0.04). Scalp cooling was very well tolerated (visual analogue scale = 79). A 45-min PICT can be recommended in 3-weekly docetaxel regimens with a dose of 75 or 100 mg/m(2), administered in 60 min. The shorter PICT is a major advantage in time investment for patients. Patients (women and men) who receive docetaxel, except combined with doxorubicin and cyclophosphamide (taxotere, adriamycin and cyclophosphamide (TAC)) should be informed about the protective effect and high tolerability of scalp cooling in avoiding CIA.

680 PREDICTION OF FAVOURABLE OUTCOME AND RATIONAL INDICATION OF DOCETAXEL RECHALLENGE IN METASTATIC CASTRATION RESISTANT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced I1 Apr 2012680 PREDICTION OF FAVOURABLE OUTCOME AND RATIONAL INDICATION OF DOCETAXEL RECHALLENGE IN METASTATIC CASTRATION RESISTANT PROSTATE CANCER Matthias Heck, Mark Thalgott, Margitta Retz, Petra Wolf, Tobias Maurer, Jürgen Gschwend, and Hubert Kübler Matthias HeckMatthias Heck Munich, Germany More articles by this author , Mark ThalgottMark Thalgott Munich, Germany More articles by this author , Margitta RetzMargitta Retz Munich, Germany More articles by this author , Petra WolfPetra Wolf Munich, Germany More articles by this author , Tobias MaurerTobias Maurer Munich, Germany More articles by this author , Jürgen GschwendJürgen Gschwend Munich, Germany More articles by this author , and Hubert KüblerHubert Kübler Munich, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.762AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To identify predictors of favourable oncological outcome in metastatic castration-resistant prostate cancer (mCRPC) patients who are treated with docetaxel rechallenge following first-line chemotherapy with docetaxel. METHODS We retrospectively evaluated the oncological outcome of mCRPC patients who were treated with 3-weekly docetaxel (75mg/m2) at first-line chemotherapy and rechallenge plus prednisone/ prednisolone. The endpoints of oncological outcome were PSA-progression-free survival (PSA-PFS) and overall survival (OS) after initiation of docetaxel rechallenge. The effect of clinical variables on PSA-PFS and OS was statistically analysed by a log-rank test or Cox regression with hazard ratios. All analyses were performed using a 0.05 level of significance. RESULTS 47 patients were included on analysis. At a median follow-up of 25.8 months (range 9.8-89.8 months) after the first administration of docetaxel, 27 (57.4%) patients had died. Median PSA-PFS was 5.9 months (95% CI 3.5-6.8 months) and median OS was 21.4 months (95% CI 18.9-23.9 months) after initiation of docetaxel rechallenge. PSA-reduction ≥ 30% was the only pre-treatment variable that correlated significantly with prolonged PSA-PFS (p=0.03) and OS (p=0.002). Patients with PSA-reduction ≥ 30% at first-line chemotherapy showed a median OS of 21.8 months since initiation of docetaxel rechallenge in comparison to 4.5 months in patients with < 30% PSA-reduction. CONCLUSIONS Docetaxel rechallenge represents an active treatment option in selected docetaxel-pretreated patients with mCRPC. In this retrospective study, PSA-reduction ≥ 30% at first-line chemotherapy with docetaxel predicted superior PSA-PFS and OS in the rechallenge setting and might, therefore, present a rational indication for docetaxel rechallenge. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e277 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthias Heck Munich, Germany More articles by this author Mark Thalgott Munich, Germany More articles by this author Margitta Retz Munich, Germany More articles by this author Petra Wolf Munich, Germany More articles by this author Tobias Maurer Munich, Germany More articles by this author Jürgen Gschwend Munich, Germany More articles by this author Hubert Kübler Munich, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Concurrent Weekly Docetaxel Chemotherapy in Combination with Radiotherapy for Stage III and IVA-B Nasopharyngeal Carcinoma

Cisplatin is the most common chemotherapeutic agent for loco-regionally advanced nasopharyngeal carcinoma (NPC); however, toxicity is a limiting factor for some patients. We retrospectively compared the efficacy and toxicity of weekly docetaxel-based and cisplatin-based concurrent chemoradiotherapy in loco-regionally advanced NPC. Eighty-four patients with Stage III and IVA-B NPCs, treated between 2007 and 2008, were retrospectively analyzed. Thirty received weekly docetaxel-based concurrent chemotherapy, and 43 were given weekly cisplatin-based concurrent chemotherapy. Radiotherapy was administered using a conventional technique (seven weeks, 2.0 Gy per fraction, total dose 70-74 Gy) with 6-8 Gy boosts for some patients with locally advanced disease. Median follow-up time was 42.3 months (range, 8.6-50.8 months). There were no significant differences in the 3-year loco-regional failure-free survival (85.6% vs. 92.3%; p=0.264), distant failure-free survival (87.0% vs. 92.5%; p=0.171), progression-free survival (85.7% vs. 88.4%; p=0.411) or overall survival (86.5% vs. 92.5%, p=0.298) of patients treated concurrently with docetaxel or cisplatin. Severe toxicity was not common in either group. Weekly docetaxel-based concurrent chemoradiotherapy is potentially effective and has a tolerable toxicity; however, further investigations are required to determine if docetaxel is superior to cisplatin for advanced stage NPC.

Prediction of favorable outcome in a docetaxel rechallenge setting in metastatic castration-resistant prostate cancer.

68 Background: To identify predictors of favourable oncological outcome in metastatic castration-resistant prostate cancer (mCRPC) patients who are treated with docetaxel rechallenge following first-line chemotherapy with docetaxel. Methods: We retrospectively evaluated the oncological outcome of mCRPC patients who were treated with 3-weekly docetaxel (75mg/m2) at first-line chemotherapy and rechallenge plus prednisone/ prednisolone. The endpoints of oncological outcome were PSA-progression-free survival (PSA-PFS) and overall survival (OS) after initiation of docetaxel rechallenge. The effect of clinical variables on PSA-PFS and OS was statistically analysed by a log-rank test or Cox regression with hazard ratios. All analyses were performed using a 0.05 level of significance. Results: 47 patients were included on analysis. At a median follow-up of 25.8 months (range 9.8-89.8 months) after the first administration of docetaxel, 27 (57.4%) patients had died. Median PSA-PFS was 5.9 months (95% CI 3.5-6.8 months) and median OS was 21.4 months (95% CI 18.9-23.9 months) after initiation of docetaxel rechallenge. PSA-reduction ≥ 30% was the only pre-treatment variable that correlated significantly with prolonged PSA-PFS (p=0.03) and OS (p=0.002). Patients with PSA-reduction ≥ 30% at first-line chemotherapy showed a median OS of 21.8 months since initiation of docetaxel rechallenge in comparison to 4.5 months in patients with &lt; 30% PSA-reduction. Conclusions: Docetaxel rechallenge represents an active treatment option in selected docetaxel-pretreated patients with mCRPC. In this retrospective study, PSA-reduction ≥ 30% at first-line chemotherapy with docetaxel predicted superior PSA-PFS and OS in the rechallenge setting and might, therefore, present a rational indication for docetaxel rechallenge.

Randomized Phase II Study of Primary Systemic Chemotherapy and Trastuzumab for Operable HER2 Positive Breast Cancer

Background In primary systemic therapy in patients with human epidermal growth factor receptor 2 positive (HER2 +) breast cancer, improvements in pathologic complete response (pCR) rate have been achieved by administering trastuzumab. Patients and Methods Patients with stage II or IIIA HER2 + operable breast cancer were randomly assigned to receive four 3-weekly cycles of FEC (5-fluorouracil 500 mg/m 2, epirubicin 100 mg/m 2, cyclophosphamide 500 mg/m 2) followed by 4 cycles of 3-weekly trastuzumab (8 mg/kg week 1 and then 6 mg/kg) with either 12 weekly doses of paclitaxel 80 mg/m 2 (FEC-PH) or 4 cycles of 3-weekly docetaxel 75 mg/m 2 (FEC-DH). Results Between March 2007 and June 2008, 102 patients were enrolled. Forty-nine patients receiving FEC-PH and 47 receiving FEC-DH were assessable for efficacy and safety. Eighty-four patients completed treatment and underwent surgery. There was no significant difference in the pCR rate between the 2 groups (46.9% [95% CI, 33.7%-60.6%] with FEC-PH vs. 42.6% [95% CI, 29.5%-56.8%] with FEC-DH; P = .67). Analysis by hormone receptor (HR) status showed pCR rates of 54.2% (32/59) in HR − tumors and 29.7% (11/37) in HR + tumors ( P = .02). Among HR − tumors, the pCR rates were 65.4% and 45.5% in patients treated with FEC-PH and FEC-DH, respectively ( P = .13). Conclusions There was no significant difference in pCR rate between FEC-PH and FEC-DH. Both regimens achieved higher pCR rates in HR − than HR + breast cancer, and there was a trend toward higher pCR in HR − tumors with FEC-PH compared with FEC-DH. Further investigation is warranted to explore the relationship between efficacy and HR status.

The End of an Era: Shall We Move Forward?

The End of an Era: Shall We Move Forward?

7053 POSTER Hormonal Impact of Second-line Salvage Chemotherapy With Carboplatin Plus Weekly Docetaxel in Patients With Castration and Docetaxel-resistant Prostate Cancer

7053 POSTER Hormonal Impact of Second-line Salvage Chemotherapy With Carboplatin Plus Weekly Docetaxel in Patients With Castration and Docetaxel-resistant Prostate Cancer

Plasma chromogranin A: Clinical implications in patients with castrate resistant prostate cancer receiving docetaxel chemotherapy

Development of castrate resistant prostate cancer (CRPC) indicates progressive disease with poor survival. Docetaxel has variable response with a good proportion of nonresponders. Neuroendocrine differentiation, hypothesised as one of the mechanisms behind development of CRPC, can be assessed by plasma Chromogranin A (CgA). We evaluated the clinical importance of circulating CgA in CRPC patients receiving Docetaxel. Plasma CgA was assessed by ELISA in 14 patients with CRPC receiving 3-weekly docetaxel. Baseline PSA, baseline CgA, PSA response, CgA response and clinical response to chemotherapy were evaluated and analysed. Increased plasma CgA was observed in 64.3% of patients. There was no correlation between baseline CgA and PSA. Two patients with PSA < 10 ng/ml had elevated CgA. Baseline CgA was not influenced by variables such as site of metastasis and time to develop CRPC status. Seven patients (50%) had PSA-response and 5 (36%) CgA-response. In 4 patients PSA response and CgA response were discordant. Compared to men with normal baseline CgA, a higher proportion of those with elevated baseline CgA had PSA response (55% vs 40%), symptomatic response (66% vs 40%) and radiological response (55% vs 20%). Two patients with symptomatic response had only CgA response. Three patients having disease progression despite PSA response had increasing CgA. CgA and PSA are complementary tumour markers in CRPC. CgA may help in predicting the response of docetaxel therapy. Rising CgA during therapy may be associated with bad prognosis whereas CgA response is likely to be associated with clinical response.

Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: Results from AVADO

BackgroundOncologic treatment in elderly patients is challenging, due to comorbidities, often impaired organ function, limited clinical trial evidence, inadequate guidelines and no consistent ‘elderly’ definition. We report exploratory sub-analyses of safety and efficacy in elderly patients, defined as ⩾65years old, in AVastin And DOcetaxel (AVADO) receiving first-line bevacizumab plus docetaxel for metastatic breast cancer (mBC). Patients and methodsPatients with HER2-negative, locally recurrent or mBC were randomised to 3-weekly docetaxel (100mg/m2) with placebo, bevacizumab 7.5mg/kg or bevacizumab 15mg/kg, for 9 cycles or until disease progression or unacceptable toxicity. Patients had no prior chemotherapy for mBC. ResultsProgression-free survival (PFS) was increased with bevacizumab in the elderly subpopulation (n=127), the effect being greater with higher dose (hazard ratio=0.63 [95% confidence interval (CI) 0.383–1.032] versus 0.76 [95% CI: 0.46–1.262], respectively). PFS was numerically similar in the elderly and overall populations, but the former failed to achieve statistical significance. Overall response rates for docetaxel plus placebo, bevacizumab 7.5mg/kg and 15mg/kg were 44.7%, 36.6% and 50.0%, respectively. Effects on survival were not statistically significant. Bevacizumab was well tolerated in elderly patients, the most common adverse effects were neutropenia and febrile neutropenia; there was no excess of grade⩾3 cardiovascular events. There was no clear correlation between baseline hypertension and its development during study treatment. ConclusionsIn this exploratory sub-analysis in AVADO, bevacizumab plus docetaxel showed efficacy in elderly patients similar to the overall study population. There were no unexpected safety signals in patients aged 65years or older.

Impact of docetaxel‐based chemotherapy on quality of life of patients with castration‐resistant prostate cancer: results from a prospective phase II randomized trial

What's known on the subject? and What does the study add? Data on quality of life during docetaxel treatment in castration resistant prostate cancer was mainly provided by SWOG and TAX327 trials. In the TAX327 trial biochemical response and pain predicted survival, whereas quality of life outcomes did not. In the present study, there were no statistically significant changes in the quality of life scales during treatment except in the case of patients receiving docetaxel and estramustine, who experienced a significant decrease in pain. Our data seem to suggest that patients with a better baseline quality of life (and consequently with fewer symptoms) are more likely to achieve a biochemical response. • To assess quality of life (QoL) outcomes and pain changes in patients affected by castration-resistant prostate cancer enrolled in a phase II randomized trial of 3-week docetaxel (DOC)-based chemotherapy. • To provide further data to clarify the conflicting published data concerning the impact of DOC on the patients' QoL. • QoL outcomes were assessed using the European Organisation for the Research and Treatment of Cancer QLQ-C30 questionnaire. • Pain changes were evaluated by means of the Brief Pain Inventory at baseline and after every two DOC courses. • The patients completing at least two questionnaires (at baseline and before the third course) were considered evaluable. • In all, 59 patients were evaluable. • Asymptomatic patients and responders had a better baseline QoL than symptomatic patients and non-responders. • There were no statistically significant changes in the QLQ-C30 scales during treatment except in the case of patients receiving DOC and estramustine, who experienced a significant decrease in pain. • There was a progressive improvement in the mean intensity and interference scores of the Brief Pain Inventory. • Our data confirm that QoL is generally maintained during chemotherapy. • There is a substantial reduction in pain. • Our results also suggest that baseline QoL may predict treatment response.

PSA response and early PSA progression evaluated in patients randomized in a phase III trial comparing androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in hormone-naive metastatic prostate cancer (GETUG-AFU 15/0403).

4524 Background: Androgen deprivation therapy (ADT) is the standard treatment of hormone naïve metastatic prostate cancer (HNMPC). We initiated a phase III multicentre trial comparing ADT with or without docetaxel (D) in HNMPC (GETUG 15) and the primary endpoint is overall survival. PSA progression defined as an increase of 25% over baseline or nadirin the first 7 months was recently shown to be a strong predictor of death in HNMPC (Hussain M et al J Clin Oncol 27: 2009). Methods: Patients (pts) with HNMPC were randomly assigned to either arm A (ADT plus D: 75mg/m² q3w, 9 cycles) or arm B (ADT). From 10/2004 to 12/2008, 385 pts were accrued. The median baseline PSA values were 29.4 ng/ml (0.05-2,170) in arm A and 25.3 ng/ml (0.1-11,900) in arm B. Data on PSA response are available in 171/192 pts (arm A) pts and 181/193 pts (arm B) at 3 months and 156 pts (arm A) and 148 pts (arm B) at 6 months. Results: A PSA response (> 30%) was achieved at 3 months in 93.6% (arm A) and 85.1% (arm B) (p=0.02). A PSA response (> 50%) was achieved at 3 months in 90.6% (arm A) versus 80.1% (arm B) (p=0.01). When assessed at 6 months, a PSA response (> 30%) was obtained in 94.9% (arm A) versus 86.5% (arm B) (p=0.02). A PSA response (> 50%) was achieved in 94.9% (arm A) versus 85.8% (arm B) (p=0.01) A PSA progression ( 25% increase) was observed in 1.3% in arm A and 10.1% in arm B (p=0.002). Conclusions: The addition of 3-weekly docetaxel to ADT significantly improves PSA response and significantly reduces PSA progression at 6 months in patients with HNMPC.

Effects on quality of life, anti-cancer responses, breast conserving surgery and survival with neoadjuvant docetaxel: a randomised study of sequential weekly versus three-weekly docetaxel following neoadjuvant doxorubicin and cyclophosphamide in women with primary breast cancer

BackgroundWeekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life. However, no studies have compared the standard three weekly regimen to the weekly regimen in terms of quality of life. The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel. Secondary aims were to determine the clinical and pathological responses, incidence of Breast Conserving Surgery (BCS), Disease Free Survival (DFS) and Overall Survival (OS).MethodsEighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were randomised to receive twelve cycles of weekly docetaxel (33 mg/m2) or four cycles of 3-weekly docetaxel (100 mg/m2). The Functional Assessment of Cancer Therapy-Breast and psychosocial questionnaires were completed.ResultsAt a median follow-up of 71.5 months, there was no difference in the Trial Outcome Index scores between treatment groups. During weekly docetaxel, patients experienced less constipation, nail problems, neuropathy, tiredness, distress, depressed mood, and unhappiness. There were no differences in overall clinical response (93% vs. 90%), pathological complete response (20% vs. 27%), and breast-conserving surgery (BCS) rates (49% vs. 42%). Disease-free survival and overall survival were similar between treatment groups.ConclusionsWeekly docetaxel is well-tolerated and has less distressing side-effects, without compromising therapeutic responses, Breast Conserving Surgery (BCS) or survival outcomes in the neoadjuvant setting.Trial registrationISRCTN: ISRCTN09184069

PSA response and early PSA progression evaluated in patients randomized in a phase III trial comparing androgen-deprivation therapy (ADT) plus docetaxel versus ADT alone in hormone-naive metastatic prostate cancer (GETUG-AFU 15/0403).

10 Background: Androgen deprivation therapy (ADT) is the standard treatment of hormone naïve metastatic prostate cancer (HNMPC). We initiated a phase III multicentre trial comparing ADT with or without docetaxel (D) in HNMPC (GETUG 15) and the primary endpoint is overall survival. PSA progression defined as an increase of 25% over baseline or nadirin the first 7 months was recently shown to be a strong predictor of death in HNMPC (Hussain M et al J Clin Oncol 27: 2009). Methods: Patients (pts) with HNMPC were randomly assigned to either arm A (ADT plus D: 75mg/m2 q3w, 9 cycles) or arm B (ADT). From 10/2004 to 12/2008, 385 pts were accrued. The median baseline PSA values were 29.4 ng/mL (0.05-2,170) in arm A and 25.3 ng/mL (0.1-11,900) in arm B. Data on PSA response are available in 171/192 pts (arm A) pts and 181/193 pts (arm B) at 3 months and 156 pts (arm A) and 148 pts (arm B) at 6 months. Results: A PSA response (&gt; 30%) was achieved at 3 months in 93.6% (arm A) and 85.1% (arm B; p=0.02). A PSA response (&gt; 50%) was achieved at 3 months in 90.6% (arm A) versus 80.1% (arm B; p=0.01). When assessed at 6 months, a PSA response (&gt; 30%) was obtained in 94.9% (arm A) versus 86.5% (arm B; p=0.02). A PSA response (&gt; 50%) was achieved in 94.9% (arm A) versus 85.8% (arm B; p=0.01) A PSA progression (25% increase) was observed in 1.3% in arm A and 10.1% in arm B (p=0.002). Conclusions: The addition of 3-weekly docetaxel to ADT significantly improves PSA response and significantly reduces PSA progression at 6 months in patients with HNMPC. No significant financial relationships to disclose.