Weekly paclitaxel (Ta) and capecitabine (Xel) in HER2 negative metastatic breast cancer (MBC):
a multicentre GINECO randomised phase II study comparing two TaXel schedules
A.Lortholary 1, A.C. Hardy-Bessard 2, T. Bachelot 3, P. Dalivoust 4, G. de Rauglaudre 5, J. Alexandre 6, H. Bourgeois 7, D. Jaubert 8, D. Paraiso 9, R. Largillier 10; GINECO Group, Paris, France (1)Centre Catherine de Sienne, Nantes, (2)Clinique Armoricaine, Saint Brieuc, (3)Centre Léon Bérard, Lyon, (4)Hôpital Saint-Joseph, Marseille, (5)Clinique Sainte Catherine, Avignon, (6)Hôpital Hôtel Dieu, Paris, (7)Centre Jean Bernard, Le Mans (8)Clinique Tivoli, Bordeaux, (9)Centre Hospitalier de l’Agglomération Montargoise, Amilly, (10)Centre Antoine Lacassagne, Nice. ABSTRACT - N°1114
BaCkGROuNd: Ta and Xel are synergistic in vitro. Compa-
sTudY dEsIGN
sTaTIsTICal aNalYsIs
red to a continuous weekly Tax combined with a classical 14 days (d)/21 Xel administration (Elza-Brown et al ASCO 2000), This is a phase II, open label, multicentre, Median dose-intensity of Taxol (mg/m²/week) was identical in both arms
Main objective
Secondary objectives
The primary endpoint of this study was to determine the propor- we have explored the combination of Xel 5d/week (wk) and prospective, randomised study. All patients tion of patients who needed a dose reduction in the first 6 months Arm A (n=66)
weekly Ta 3 wk out of 4 with the objective of increasing the of the treatment or a delay more than 1 week in one cycle related Patients
(standard schedule - every 21 days)
efficacy/toxicity ratio of the TaXel combination.
to a grade 3-4 toxicity according to CTCAE.
with Good Clinical Practice Guidelines.
The sample size of this study was based on estimates of dose treated with anthracycline ± docetaxel were randomised Arm B (n=64)
reduction rate of about 75%. On the basis of a predicted attrition either to A: Ta (60 mg/m²/w) + Xel (2000 mg/m²/d x 14 d/21) (experimental schedule - every 28 days)
rate of 15%, α risk = 0.05 (type I error) and β = 0.20 (type II error), or to B: Ta (80 mg/m²/w) + Xel (2000 mg/m²/d x 5 d/wk) 3wk Number of patients: n=130
a total of 130 patients were needed (65 per arm) for the study. REsulTs: From 01/2006 to 01/2008, 130 pts were accrued
(A 66, B 64). Pt characteristics were well balanced between
the two arms including median age (58 yrs), histologic type
and grade, hormone receptor-positive tumour (80%), previous treatment, visceral disease (72%), number of sites (>1; 63%), PaTIENT dEMOGRaPHICs
ECOG PS (0; 42%, 1; 58%). Pts received a median of 6 cycles (1-23) with a received/planned mean dose of 89.3% for Ta in From 01/2006 to 01/2008, 130 patients were accrued (66 in Arm A Objective response rate was not significantly different between both arms and of 74 and 76% for Xel respectively in arm A and 64 in Arm B). Patient (Pt) characteristics were well balanced The PRiMARy oBjEcTivE of the study was met:
the two arms (44% in arm A vs 52% in arm B, p=0.524). and B. Haematological toxicity (Tox) was low in both arms with There is significantly less dose reduction throughout the first neutropenia Gr 3 in only 8% of cycles, G-CSF support in 2% 6 cycles in patients treated in arm B (67%) compared A progression-free survival advantage was seen in arm B over A of cycles and infection G3 in 5 pts. Alopecia G2 was less Patient and disease characteristics
(12 vs 9 months, p=0.172), including in the triple negative patient frequent in arm A (29 vs 60%). Other Tox were similar in both subset (n=26 patients) (6.5 vs 4.9 months, p=0.07) (Figures 1 & 2). Dose reductions
arms: [G2/3 (%) cutaneous (35/17), pain (36/9), fatigue (26/13), Fig.1: Progression free survival of the whole population
neuropathy (20/3), diarrhoea (15/6), mucositis (8/2), vomiting (Kaplan-Meier)
(9/1)] but treatment interruption due to Tox was more frequent in A (A 19, B 7 pts) (p=0.02). Response rate was 52% (B) vs 44% (A). A progression-free survival advantage was seen CONClusION
for B over A (366 vs 272 days, p=0.15) including in the triple 7.5-10.7
negative pt subset (n = 26 pts) (197 vs 150 days, p=0.07).
The intermittent TaXel schedule
CONClusION: The intermittent schedule (3 wk out of 4)
Delayed cycles rates were similarly reported in arm A (58%) compared (weekly taxol 3/4 weeks and Xeloda
of weekly paclitaxel and capecitabine 5d/week is a well 5d/wk concomitant with Taxol admi-
a- censored
accepted, safe and effective TaXel regimen and might be nistration) was found to have a more
B- censored
a chemotherapy regimen of choice in MBC including triple ropor
favorable benefit/risk ratio than the
standard TaXel schedule (continuous
Treatment discontinuations due to toxicity were significantly more weekly Taxol and d1-14 Xeloda):
frequent in arm A (29%) than in arm B (8%) (p=0.02). The difference between the 2 arms is mainly due to non-haematological toxicity A better tolerance (less dose re-
(A=26% of the pts, B = 8%), including hand-foot syndrome (A = 12%, duction & early treatment stopping)
And a trend for better efficacy in
Hospitalisation for toxicity was required for 14% and 3% of the patients term of progression-free survival
The combination of a Taxane and Capecitabine has These encouraging results in favor
demonstrated a synergic effect and significant antitumour Fig.2: Progression free survival of the triple negative subset
of the intermittent TaXel schedule
activity in patients with advanced breast cancer.1,2 Treatment-related grade 3/4 - Adverse Events and supportive treatments
population (Kaplan-Meier)
were also found in the triple nega-
Paclitaxel (175 mg/m² q3w) combined with a classical tive population warranting further
14 days/21 Xel administration (standard schedule) showed studies in this subset of MBC
excellent efficacy (Objective Response Rate: 52%; Time To patients.
Progression: 8.1 months) in a phase II study in metastatic However, this schedule of Ta in combination with Xel was a- censored
associated with significant toxicities (particularly hand-foot Abbreviations: ER, oestrogen receptor, PR, progesterone receptor, RH, receptor hormone the patients in arm A and B, respectively.
B- censored
1- O’Shaughnessy J et al, JCO. 2002 Jun TREaTMENT EXPOsuRE
excellent efficacy/safety ratio in phase I.3 A total of 414 and 402 cycles of paclitaxel and capecitabine were The purpose of this study was to explore the efficacy/ administered to 66 patients in arm A and 64 in arm B, respectively. toxicity safety of the combination of Xel 5d/week (wk) Patients received a median of 6 cycles (range 1 to 23 cycles) with and weekly Ta 3 wk out of 4 compared to a continuous a received/planned mean dose of 89% for Ta in both arms and 75% weekly Tax combined with a classical 14 days (d)/21 Xel for Xel in both arms in patients who were on treatment.
18.00 Months
administration (standard schedule) in patients with MBC.
Supported by Roche France


April_may-12 [1-2] final by sathyavathi.p65

Code No: R9501 Jawaharlal Nehru Technological University Hyderabad B.Pharmacy III Year II Semester Examinations April/May-12 April/May - 2012 Answer any FIVE Questions All Questions carry equal marks Discuss the role of parameters like lipophilicity, chelation and hydrogen bonding in biological activity ofdrug. Explain the concept of prodrug with examples. Write the

Microsoft word - nurse midwife-certified.doc

DOWNRIVER COMMUNITY SERVICES NURSE MIDWIFE - CERTIFIED POSITION DESCRIPTION I. OVERALL DESCRIPTION OF DUTIES AND RESPONSIBILITIES In collaboration with an obstetrician, provides primary obstetrical/gynecological healthcare to essentially normal women, including prenatal care, postpartum care, gynecological care and family planning within the scope of training and in accordance wit

Copyright ©2018 Drugstore Pdf Search