07 junio 2010
C.N. RC7 Organiza la Travesia a Nado del Estrecho de Gibraltar a Favor del Myeloma Multiple .
Colaborando con AEAL ( Asociación Linfoma - Mieloma y Leucemia ) http://www.aeal.es/ Más informacion :
http://clubnatacionrc7.com/
Yondelis Combinado con Doxil para Cáncer de Ovario en ASCO : Nuevos Datos sobre el Estudio OVA - 301 .
Presentado Domingo 6 de Mayo :Extending platinum-free interval (PFI) in partially platinum-sensitive (PPS) patients (pts) with recurrent ovarian cancer (ROC) treated with trabectedin (Tr) plus pegylated liposomal doxorubicin (Tr+PLD) versus PLD alone: Results from a PPS cohort of a phase III study.
Abstract No: 5012
Author(s): A. Poveda, S. Tjulandin, B. Kong, M. Roy, S. Chan, E. Filipczyk-Cisarz, H. Hagberg, C. Lebedinsky, T. V. Parekh, B. J. Monk; Instituto Valenciano de Oncologia, Valencia, Spain; N. N. Blokhin Russian Cancer Research Center, Moscow, Russia; Qilu Hospital, Shandong University China, Jinan City, China; CHUQ Pavillon Hotel-Dieu, Quebec, QC, Canada; Nottingham University Hospital, Nottingham, United Kingdom; Dolnoslaskie Centrum Onkologii, Wroclaw, Poland; Akademiska Sjukhuset, Uppsala, Sweden; PharmaMar, Colmenar Viejo, Madrid, Spain; Ortho Biotech Oncology Research and Development, Raritan, NJ; University of California, Irvine Medical Center, Orange, CA
Abstract:
Background: OVA-301, a phase III study comparing Tr+PLD vs. PLD alone in 672 ROC pts progressing after one prior platinum-based regimen, showed significantly longer progression-free survival (PFS), higher response rate (RR) for the combination by 3 separate assessments: independent radiology (IR), independent oncology (IO) and investigators (IA) and a positive trend for longer survival (OS) (Monk, Ann Oncol 2008 vol 19 Sup8). Methods: PFI > 6 mo was found in 430 (64%) of 672 randomized pts, including 214 (32%) pts with PPS disease (PFI 6-12 mo). Outcomes of this nonplatinum combination on PFS, RR and OS (protocol-specified interim analysis, cutoff May 08) are shown for the PPS population. We evaluated time from randomization to subsequent platinum (SP) and survival time from SP.
Results: Baseline characteristics of pts with PPS were balanced and consistent with those of the overall study population. Median (med) no. cycles, 6 (Tr+PLD) vs. 5 (PLD); 40% vs. 24% pts received ≥ 7 cycles. RR and PFS by IR significantly favored Tr+PLD: 33% vs. 15% (p = 0.0041); med PFS 7.4 vs. 5.5 mo (HR 0.65; p = 0.0152), with consistently superior outcomes by both IO and IA. Med OS from randomization was in favor of Tr+PLD: 20.7 vs. 17.2 mo (HR: 0.59; p=0.0090). Proportion of pts receiving SP was comparable in both arms. A significant delay in the administration of SP with the combination (med 15.3 vs. 11.6 mo; HR 0.60, p = 0.0093) was observed. Med survival time from start of SP until death or last contact was 11.0 vs. 9.2 mo (HR 0.72, p = 0.2480). The Tr+PLD safety profile of PPS cohort agreed with that of the overall study population and was consistent with known toxicities of each agent. No new or unexpected toxicities were seen.
Conclusions: In the PPS cohort of OVA-301, Tr+PLD induced significantly superior RR, PFS and OS (3.5 mo prolongation in med OS). Significant delay in time to SP and longer survival after SP therapy was seen after this nonplatinum regimen. Safety was manageable rendering a highly favorable benefit/risk ratio in this population with high unmet need for new therapeutic options.
Aplidin en ASCO : Plitidepsin cardiac safety analysis.
Presentado Domingo 6 de Mayo :
Plitidepsin cardiac safety analysis.
Abstract No: e13599
Author(s): A. Soto-Matos, S. Szyldergemajn, S. Extremera, B. Miguel-Lillo, V. Alfaro, C. Coronado, P. Lardelli, E. Roy, C. S. Corrado, C. M. Kahatt; PharmaMar, Colmenar Viejo, Madrid, Spain
Abstract:
Background: Plitidepsin (Aplidin, APL) is a cyclic depsipeptide of marine origin in phase II/III development in cancer patients (pts). It induces apoptosis through rapid and sustained JNK activation. Some depsipeptides have been linked to increased cardiac toxicity. Methods: Clinical databases were searched for cardiac adverse events (CAEs) in studies with single-agent APL as of Nov08. Demographic, clinical, and pharmacological variables were explored by univariate and multivariate regression logistic analysis.
Results: Forty-six of the 578 pts (8.0%) treated had at least 1 CAE; of these 1.9% (11) were APL-related. No fatal cases occurred. CAEs were classified into 3 main groups. The most frequent were rhythm abnormalities (RA) (n=31; 5.4%), whereas atrial fibrillation (AF)/flutter accounted for most cases (n=15; 2.6%). Of note, no cases of life-threatening ventricular arrhythmias occurred. The myocardial injury events (MI) (n=17; 3.0%) included possible ischemic related events as well as non-ischemic events. Finally, miscellaneous (M) (n=6; 1.0%) included all other CAEs that did not fit in neither prior one. None of the M events was related to APL. Significant associations were found with prostate or pancreas cancer diagnosis (p=0.002), known baseline cardiac risk factors (p=0.002), myalgia at baseline (p=0.004), lower Hgb levels (p= 0.006) and grade ≥ 2 hypokalemia (p=0.006). Treatment-related variables, such as APL dose, N of cycles or schedule did not result in any association. ECGs performed before and after APL administration (n=136) did not show any relevant effect on QTc interval. None of the PK parameters analyzed (Cmax and AUC from day 0 to day 28) had any significant impact on the probability of developing a CAE.
Conclusions: The most frequent type of CAEs observed were AF/atrial flutter, although its incidence was not different to what is reported in age-matched healthy population. All other type of CAEs were rare. No dose- cumulative pattern was observed; moreover, no treatment-related variables were associated with CAEs. Relevant risk factors identified were related to pts condition and/or disease-related characteristics rather than to drug exposure. Data available on 578 adult pts with advanced cancer treated with singe-agent APL supports a safe cardiac profile.
Yondelis en ASCO : Surgery of Residual Disease of Myxoid Liposarcoma Patients Responding to Yondelis .
Presentado Domingo 6 de Mayo :
Surgery of Residual Disease of Myxoid Liposarcoma Patients Responding to Trabectedin.
Abstract No: 10056
Author(s): R. Sanfilippo, F. Grosso, M. D'Incalci, P. Dileo, S. Pilotti, C. Morosi, M. Fiore, J. C. Tercero, A. Gronchi, P. G. Casali; Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; ASO Alessandria, Alessandria, Italy; Istituto di Ricerche Farmacologiche, Milan, Italy; Istituto Nazionale dei Tumori, Milano, Italy; PharmaMar, Colmenar Viejo, Madrid, Spain
Abstract:
Background: Our single-institution series, now including 53 metastatic MLS patients (pts) treated with trabectedin (T), was reviewed focusing on the use of surgery of residual disease. Methods: Since September 2002, 53 pts with metastatic pretreated MLS received T. Median age at T start was 48 yrs (range 27-77). T was given as a 24-hr continuous infusion every 21 days, at a dose between 1.0 to 1.5 mg/sqm.
Results: 578 courses were delivered (median = 10/pt). RECIST response rate was 50%, the median TTP was 15 months (90% CI = 9-18) and OS was 48 months. Eighteen pts stopped T on their best response (2 CR, 10 PR, 6 MR/SD): 10 remained in follow-up after a median of 11 courses and 8 underwent surgery of residual disease after a median of 12 courses. The decision whether to do surgery was based on resectability and extent of metastatic disease. Surgery was complete in all cases. Median TTP from treatment start was 30 and 25 months, respectively, in surgically and non-surgically treated pts. TTP was 14 months from treatment end in both groups. At a median follow-up of 29 months from treatment end, 13 pts relapsed (7 and 6 in the two subgroups). Twelve of these pts were rechallenged with T, obtaining 2 CR, 5 PR and 5 SD (median PFS = 14 months).
Conclusions: T provides prolonged tumor control in MLS. Surgery of residual disease in responding pts is an option. However, in this small series it did not seem to provide any major advantage, in the face of a selection bias favouring in principle operated pts. T rechallenge at progression in pts who stopped their treatment on best response was associated with significant further tumor control. Prospective studies to define optimal management of MLS pts responding to T are warranted.
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