Orlando, 1 giugno 2009TUMORE DEL SENO TRIPLO NEGATIVO METASTATICO: GRANDE ATTENZIONE PER GLI INIBITORI DI PARP
Dall’ASCO grande rilievo allo studio presentato da O’Shaughnessy sui farmaci inibitori di PARP che associati a chemioterapia sono stati in grado di quintuplicare il beneficio clinico della chemioterapia, indotto una regressione di oltre tre volte e raddoppiato la sopravvivenza (vs chemio) in donne con tumore del seno triplo negativo metastatico (TNBC).
Questo tipo di tumore e’ molto aggressivo e presenta aspetti comuni con il tumore BRCA1 dal punto di vista molecolare e patologico. Le neoplasie BRCA1 correlate si dimostrano sensibili all’inibitore di PARP1, un enzima di proliferazione cellulare e riparatore del DNA: questo rappresenta il razionale per intervenire con una terapia mirata con gli inibitori di PARP su donne con TNBC metastatico.
Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial.
Author(s): J. O’Shaughnessy, C. Osborne, J. Pippen, M. Yoffe, D. Patt, G. Monaghan, C. Rocha, V. Ossovskaya, B. Sherman, C. Bradley; Baylor Sammons, Texas Oncology, US Oncology, Dallas, TX; Cancer Centers of North Carolina/US Oncology, Raleigh, NC; Texas Oncology Cancer Center, US Oncology, Austin, TX; Kansas City Cancer Center, US Oncology, Kansas City, MO; BiPar Sciences, Inc., Brisbane, CA
Background: TNBC is an aggressive breast cancer subtype that shares molecular and pathologic features with BRCA1-related breast cancers. BRCA-deficient cells are sensitive to inhibition of PARP1, a critical enzyme of cell proliferation and DNA repair, and thus represent a rational target of PARP inhibitor-based cancer therapy. The objectives of this study were to evaluate BSI-201, a potent PARP1 inhibitor, in combination with gemcitabine/carboplatin (G/C) in subjects with metastatic TNBC. Methods: Eligible subjects had measurable disease and had ≤2 prior cytotoxic regimens for ER-, PR-, and HER2-negative metastatic breast cancer. Patients were randomized (1:1) to G/C alone or G/C + BSI-201. Gemcitabine (1000 mg/m2) and carboplatin (AUC=2) were given on days 1 and 8, and BSI-201 (5.6 mg/kg; iv; biweekly) on days 1, 4, 8, and 11 every 21 days. Endpoints were clinical benefit rate (CBR = CR + PR + SD ≥6 months), progression-free survival (PFS) and overall survival (OS). Results: Analyses of the first 86 of a planned 120 patients showed that BSI-201 + G/C had improved CBR, median PFS, and median OS, compared with G/C alone. The frequency and nature of adverse events (AEs) did not differ between arms. Conclusions: This preliminary analysis demonstrates that BSI-201 + G/C significantly improves CBR, PFS, and OS, compared with G/C alone. BSI-201 + G/C was well tolerated, with BSI-201 adding no significant toxicity to G/C. Updated CBR, PFS, and OS for all 120 patients and exploratory correlative analyses of PARP expression and clinical response will be presented.
PREVENZIONE: ALTO IL RISCHIO DI FALSI POSITIVI NELLA TOMOGRAFIA PER IL TUMORE DEL POLMONE
Ricercatori del National Cancer Institute di Bethesda hanno voluto misurare il rischio di falsi positivi fra pazienti che si sono sottoposti a due esami di screening per tumore al pomone con tomografie computerizzate a basse dosi. Sono stati presi in esame 1.610 pazienti: la probabilita’ cumulativa di falsi positivi e’ risultata del 21% dopo il primo screen, del 33% dopo il secondo. Questo rischio e’ invece risultato, rispettivamente, del 9 e del 15% nei 1.580 pazienti sottoposti a due radiografie toraciche.
Cumulative risk for a false-positive test using low-dose computed tomography in lung cancer screening
Author(s): J. M. Croswell, S. G. Baker, P. M. Marcus, J. D. Clapp, B. S. Kramer; National Institutes of Health, Bethesda, MD; National Cancer Institute, Bethesda, MD; IMS, Incorporated, Rockville, MD
Background: Screening with low-dose computed tomography (LDCT) has been promoted as the best hope for curing lung cancer. However, cumulative false-positive (FP) rates have never been formally reported. We quantified the cumulative risk of receiving ≥1 FP test for individuals in a lung cancer screening program with 2 annual screens. Methods: Prior to the ongoing National Lung Screening Trial (NLST), a definitive randomized controlled trial of LDCT versus single-view chest xray (CXR), a randomized controlled feasibility trial was conducted at six NLST centers. Participants (55-74 years at entry, current or former smokers, and ≥ 30 pack/year smoking history) were offered a baseline LDCT (N = 1,610) or CXR (N = 1,580), and one repeat annual screen, and were followed for 1 year after their final screen. Participants who received at least one screening exam were eligible for this analysis. Exclusion criteria included chest CT in the past 24 months or history of lung cancer. A positive screen was any noncalcified nodule ≥ 4mm or other radiographic finding deemed suspicious for cancer. A FP was a positive screen with: 1) a completed negative work-up, or 2) ≥ 12 months follow-up with no cancer diagnosis. Results: Using a Kaplan-Meier analysis, an individual’s cumulative probability of ≥ 1 FP LDCT was 21% (95% CI, 19%-23%) after one screen and 33% (95% CI, 30%-35%) after two. The cumulative probability of ≥ 1 FP CXR was 9% (95% CI, 8%-11%) and 15% (95% CI, 13%-16%) after one and two screens, respectively. On multivariable analysis, higher odds of FP for LDCT were associated with increased participant age (>64 years) (OR 1.34, 95% CI, 1.04-1.73); current versus former smoker status trended toward higher FP odds (OR 1.22, 95% CI, 0.95-1.56). 6.6% of participants with a FP LDCT underwent an invasive diagnostic follow-up procedure; 1.6% had major surgery. 4.2% of participants with a FP CXR underwent an invasive diagnostic follow-up procedure; 1.9% had major surgery. Conclusions: Risks of LDCT FP are substantial after only two annual examinations; the potential resulting economic, psychosocial, and physical burdens of this modality warrant investigation.
TUMORE DELLA PROSTATA, BUONI I RISULTATI DELL’ MDV3100
Uno studio di fase I/II condotto dal Prostate Cancer Clinical Trials Consortium ha valutato l’efficacia e la tollerabilita’ di MDV3100, un antagonista del recettore degli androgeni di seconda generazione. Si e’ riscontrata un’attivita’ antitumorale in carcinoma prostatico resistente alla castrazione con dosi multiple fino a un massimo di 240mg per giorno. L’evidenza e’ basata sulla riduzione dei livelli di PSA, sulla radiologia e sulle cellule tumorali circolanti.
Antitumor activity of MDV3100 in a phase I/II study of castration-resistant prostate cancer (CRPC).
Author(s): H. I. Scher, T. M. Beer, C. S. Higano, M. Taplin, E. Efstathiou, A. Anand, D. Hung, M. Hirmand, M. Fleisher, The Prostate Cancer Clinical Trials Consortium; Memorial Sloan-Kettering Cancer Center, New York, NY; Oregon Health & Science University, Portland, OR; University of Washington c/o SCCA, Seattle, WA; Dana-Farber Cancer Institute , Boston, MA; University of Texas M. D. Anderson Cancer Center, Houston, TX; Memorial Sloan-Kettering Cancer Center , New York , NY; Medivation, Inc., San Francisco , CA; Medivation, Inc. , San Francisco , CA
Background: MDV3100 is a novel AR antagonist selected for activity in prostate cancer model systems with overexpressed AR. In contrast to bicalutamide, MDV3100 blocks nuclear translocation of AR and DNA binding, and has no known agonist activity when AR is overexpressed. Antitumor activity of MDV3100 in a Phase I/II trial was assessed by prostate-specific antigen (PSA), soft tissue and osseous disease, circulating tumor cells (CTC), and time on treatment. Methods: Patients (pts) with progressive CRPC were enrolled in sequential cohorts of 3-6 pts at 30, 60, 150, 240, 360, 480 and 600 mg/day. Once the safety of a dose was established, enrollment was expanded at doses >60 mg/day to include 12 chemotherapy-naïve (naïve) and 12 post-chemotherapy pts per cohort. Results: 140 pts were enrolled. 114 pts at 30-360 mg/day have been followed for >12 weeks. PSA declines (>50% from baseline) were observed at week 12 in 57% (37/65) of naïve and 45% (22/49) of post-chemo pts. Data suggest a dose-response trend particularly in post-chemo pts where PSA responses were 32% at 60 and 150 mg/day and 58% at 240 and 360 mg/day. At 12 weeks, radiographic control (no progression) was observed in 35/47 pts (74%) with evaluable soft tissue lesions per PCWG2 guidelines and 50/81 pts (62%) with bone lesions. CTC counts on 101 of 114 pts showed 92% (56/61) with favorable (<5) counts pretreatment maintained favorable posttreatment counts, while 53% (21/40) converted from unfavorable to favorable posttreatment. For post-chemo pts, favorable retention was 100% (17/17) and unfavorable to favorable conversion at 240 and 360 mg/day was 60% (6/10). 87 pts at 30-240 mg/day have been followed for >24 weeks; 35 (40%) received treatment >24 weeks. At 600 mg/day, 2 of 3 pts had dose limiting toxicity (rash; seizure). Dose reductions due to fatigue were noted at 480 and 360 mg/day. Conclusions: MDV3100 is a promising candidate for the treatment of prostate cancer assessed by PSA, imaging, CTC, and time on treatment. The data suggest a dose-response trend and consistency across endpoints. Pt follow-up is continuing. The efficacy comparable to that at higher doses and the better adverse event profile, led to the selection of 240 mg/day as the recommended dose for a phase III trial in CRPC.
TUMORE DEL RENE
Vengono presentati al Congresso i risultati finali di uno dei grandi studi dedicati al carcinoma renale metastatico. I risultati sono favorevoli, anche in termini di risposte obiettive e PFS, mentre vi e’ solo un trend a favore di un’aumentata sopravvivenza. La combinazione di bevacizumab e interferone rimane una delle opzioni terapeutiche in questa situazione.
Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon-α2a (IFN) in metastatic renal cell carcinoma (mRCC).
Author(s): B. J. Escudier, J. Bellmunt, S. Negrier, B. Melichar, S. Bracarda, A. Ravaud, S. Golding, S. Jethwa, on behalf of the AVOREN Investigators; Institut Gustave Roussy, Villejuif, France; University Hospital del Mar, Barcelona, Spain; Centre Léon Bérard, Lyon, France; Palacký University Medical School , Olomouc, Czech Republic; Medical Oncology, Perugia, Italy; Hôpital Saint André, CHU, Bordeaux, France; F. Hoffmann-La Roche, Basel, Switzerland
Background: In the AVOREN trial, BEV (Avastin) + IFN significantly improved PFS and ORR compared with placebo + IFN in pts with mRCC [Escudier, Lancet. 2007]. The study was unblinded after interim analysis due to significant superiority of BEV + IFN and the DSMB recommended crossover of pts from placebo to BEV (n = 13). We report here the results of the final analysis. Methods: Eligible pts had predominantly clear-cell mRCC, prior nephrectomy, no prior systemic therapy for metastatic disease, KPS ≥70%, no CNS metastases and adequate organ function. Pts were randomised to IFN (9MIU tiw) + BEV (10 mg/kg q2w) or placebo until disease progression. Primary endpoint was OS, with pre-planned stratified and unstratified analyses according to regional regulatory requirements. Results: 649 pts were randomised to BEV + IFN (n = 327) or placebo + IFN (n = 322). An independent radiological review confirmed previous investigator assessments, showing PFS of 10.4 vs 5.5 months (HR 0.57) and a response rate of 31% vs 12% in the two arms, verifying the robustness of the investigator analysis. At the time of final OS analysis (444 events), median follow-up was 22.9 months in the BEV arm and 20.6 months in the placebo arm. Final median OS stratified for region and Motzer score was 23.3 months in the BEV + IFN arm and 21.3 months in the IFN + placebo arm (HR 0.86 [95% CI: 0.72-1.04], p = 0.1291). No new or unexpected AEs were observed. More pts in the IFN + placebo arm than the BEV + IFN arm received post-protocol therapy, including TKIs, mTOR inhibitors, cytokines and chemotherapy: 180 (55%) in the BEV + IFN arm and 202 (63%) in the IFN + placebo arm. Exploratory analysis showed that median OS in pts receiving second-line TKI therapy (BEV + IFN, n = 96; IFN + placebo, n = 81) was 38.6 months vs 33.2 months (HR = 0.77 [95% CI: 0.51-1.15], p = 0.1948). Further subgroup analyses will be presented. Conclusions: BEV + IFN is a first-line standard of care for pts with mRCC, improving PFS and ORR, with a trend toward improved OS, compared with IFN. The observed OS results may have been influenced by subsequent anti-neoplastic therapy, which was not prespecified in the protocol and represents an uncontrolled element of the OS analysis.
SPECIALE GI CANCER
Di seguito gli studi presentati all’ASCO sui tumori gastrointestinali ritenuti fra i piu’ meritevoli di attenzione:
•Surgery unnecessary for majority of patients with advanced colorectal cancer: Most patients with metastatic colorectal cancer can safely avoid surgery on their primary tumors.
Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment
G. A. Poultsides, E. L. Servais, L. B. Saltz, S. Patil, N. E. Kemeny, J. G. Guillem, M. Weiser, L. K. Temple, W. Wong, P. B. Paty
Background:In the absence of symptoms (bleeding, perforation, obstruction) or resectable metastatic disease, primary tumor resection in patients who present with synchronous metastatic colorectal cancer (CRC) is of uncertain benefit. The purpose of this study was to describe the frequency of intervention necessary to palliate the intact primary tumor in patients who present with synchronous stage IV CRC and receive up-front modern combination chemotherapy without prophylactic surgery. Methods: Using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (FOLFOX, IFL, or FOLFIRI) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. Results: Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (stent or radiotherapy), whereas 213 (89%) never required any direct symptomatic management for their intact primary. Of those, 47 (20%) ultimately underwent elective colon resection at the time of metastasectomy and 8 (3%) during laparotomy for hepatic artery infusion pump placement. Neither use of bevacizumab, location of the primary tumor in the rectum, or metastatic disease burden were associated with increased intervention rate. In addition, when included as a time-varying covariate in a Cox regression model, the need for emergent intervention did not correlate with overall survival. Conclusions: Most patients with synchronous stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease. Disclosures:Leonard Saltz,,Consultant or Advisory Role,PfizerLeonard Saltz,,Consultant or Advisory Role,GenentechLeonard Saltz,,Consultant or Advisory Role,Bristol MyersLeonard Saltz,,Consultant or Advisory Role,ImcloneLeonard Saltz,,Consultant or Advisory Role,AmgenLeonard Saltz,,Research Funding,ImcloneLeonard Saltz,,Consultant or Advisory Role,RocheLeonard Saltz,,Research Funding,GenentechLeonard Saltz,,Research Funding,PfizerLeonard Saltz,,Research Funding,RocheLeonard Saltz,,Research Funding,Bristol MyersLeonard Saltz,,Research Funding,AmgenNancy Kemeny,,Research Funding,Sanofi-AventisNancy Kemeny,,Honoraria,Sanofi-AventisNancy Kemeny,,Research Funding,Pfizer
•Trial compares common adjuvant treatments for pancreatic cancer: A phase III trial comparing the adjuvant treatments most commonly used for pancreatic cancer in the United States and Europe (gemcitabine and 5- FU/FA, respectively) found that there is no difference in survival between the two regimens, though gemcitabine was associated with fewer side effects.
ESPAC-3(v2) – A multicentre, international, open label, randomised controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma
J. Neoptolemos, M. Büchler, D. D. Stocken, P. Ghaneh, D. Smith, C. Bassi, M. Moore, D. Cunningham, C. Dervenis, D. Goldstein, The European Study Group for Pancreatic Cancer (ESPAC)
Background:Adjuvant 5-FU/FA (ESPAC-1 trial) and recently, adjuvant GEM (CONKO-001 trial) have demonstrated improved survival for patients with resected pancreatic cancer. The aim of the ESPAC-3 (v2) trial was to compare 5FU/FA vs GEM to identify if either adjuvant chemotherapy was associated with significantly better survival. Methods: Patients with either an R0 or R1 resection for pancreatic ductal adenocarcinoma were randomised (stratified for resection margin status and country) within 8 weeks of surgery to receive either 5FU/FA (FA, 20 mg/m2, iv bolus injection followed by 5-FU, 425 mg/m2, iv
bolus injection given 1-5d every 28 days) or GEM (1000 mg/m2 iv infusion 1d, 8d and 15d every 4 weeks) for 6 months. The primary outcome measure was overall survival; the secondary measures were toxicity, progression free survival and quality of life. 1030 patients were needed to detect a 10% difference in 2- year survival rates with 90% power. Results: 1088 patients from 16 countries were randomised between 11th July 2000 and 12th Jan 2007 (551 5FU/FA, 537 GEM). Median (range) age was 63 (31-85) years, 598 (55%) were men. Median tumour size was 30 (20-350) mm, 384 (35%) were R1 resections, 777 (72%) were node positive and 263 (25%) were poorly differentiated tumours. Final analysis will be carried out with a minimum of 2 years follow-up (data lock 12th Jan 2009). The current overall number of deaths is 698 (64%). Analysis of the primary outcome will be based on all cause mortality using log-rank analysis on an intention to treat basis. Cox proportional hazards modelling, or alternative, will be used to adjust any treatment effect by stratification factors at randomisation and other known prognostic factors. Conclusions: This is the largest adjuvant trial ever conducted for pancreatic ductal adenocarcinoma and the results will be reported in full at the meeting. Disclosures:John Neoptolemos,,Consultant or Advisory Role,PfizerJohn Neoptolemos,,Research Funding,PharmexaJohn Neoptolemos,,Research Funding,Oxford BiomedicaJohn Neoptolemos,,Research Funding,Cytimmune
•The largest study to date on anal cancer supports the current standard: A phase III study finds that the current standard of care for anal cancer should not be changed, and that ongoing maintenance therapy after initial treatment is not effective.
A randomised trial of chemoradiation using mitomycin or cisplatin, with or without maintenance cisplatin/5FU in squamous cell carcinoma of the anus (ACT II)
R. James, S. Wan, R. Glynne-Jones, D. Sebag-Montefiore, L. Kadalayil, J. Northover, D. Cunningham, H. Meadows, J. Ledermann, National Cancer Research Institute (NCRI) ACT II Trial Management Group
Background:Chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is standard treatment for anal cancer. The ACT II trial addresses two research questions: whether (i) replacing MMC with cisplatin (CDDP) improves the complete response (CR) rate, and (ii) two cycles maintenance chemotherapy (with 5-FU and CDDP) after CRT reduces recurrence. Methods: Between 2001 and 2008, 940 patients (pts) were recruited to a multi-centre, randomised factorial trial. They received 5-FU (1000mg/m2/day on days 1-4 and 29-32), radiotherapy (50.4 Gy in 28 fractions), and were randomised to receive in addition either MMC (12 mg/m2, day 1; n=471) or CDDP (60 mg/m2 on days 1 & 29; n=469). Pts were also randomised to receive maintenance therapy (n=448) 4 weeks after CRT with two cycles of CDDP and 5-FU in weeks 11 and 14, or no maintenance (n=446). Maintenance randomisation was not considered appropriate in 46 pts. The trial was powered to detect a difference in the CR rate of 5% (CDDP vs MMC), and 30% reduction in recurrence (maintenance vs no maintenance); ≥80% power. Clinical response was assessed at 11 & 18 weeks, and by CT at 26 weeks. Median follow-up is currently 2.5 years. Results: The median age was 58 yrs; 62% male, 38% female; tumour site – canal (81%), margin (15%), not known (N/K) (4%); stage T1-T2 (50%), T3-T4 (43%), N/K (7%); node negative (62%), positive (30%)), N/K (8%). The CR rate was 91% in both CDDP and MMC arms: difference -0.1% (95% CI -4.4, +4.1, p=0.96). CDDP pts had fewer acute grade 3/4 haematological toxicities (12 vs 25%, p<0.001). Follow up data will be mature enough for the maintenance comparison in March 2009 for a logrank analysis of the recurrence rate. Disease-free, colostomy-free and overall survival, and toxicity, will be reported for both comparisons. Conclusions: ACT II is the largest trial ever conducted in anal cancer. Very high response rates and excellent tolerability can be achieved with this CRT schedule.Disclosures:Rob Glynne-Jones,,Other Remuneration,RocheRob Glynne-Jones,,Honoraria,Merck-SeronoRob Glynne-Jones,,Research Funding,RocheRob Glynne-Jones,,Honoraria,PfizerRob Glynne-Jones,,Other Remuneration,AstraZenecaRob Glynne-Jones,,Other Remuneration,Merck SeronoRob Glynne- Jones,,Research Funding,Merck SeronoRob Glynne-Jones,,Research Funding,Sanofi AventisRob Glynne-Jones,,Honoraria,RocheRob Glynne-Jones,,Other Remuneration,PfizerRob Glynne-Jones,,Honoraria,Sanofi Aventis.
•Oxaliplatin does not improve outcomes for rectal cancer: Adding oxaliplatin to standard treatment in patients with locally advanced rectal cancer does not improve tumor response. A preliminary analysis suggests the treatment may reduce distant metastases, however.
Preoperative fluorouracil (FU)-based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: Pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)-01 randomized phase III trial
C. Aschele, C. Pinto, S. Cordio, G. Rosati, A. Tagliagambe, S. Artale, P. Rosetti, S. Lonardi, L. Boni, L. Cionini, on behalf of STAR Network Investigators
Background:Oxaliplatin (OXA) enhances the efficacy of FU-based chemotherapy in colon cancer. This randomized phase III trial investigated the effect of adding OXA to preoperative (preop) FU-based pelvic chemoradiation (CRT) in patients (pts) with locally-advanced rectal cancer. Methods: Eligibility required a resectable, biopsy-proven rectal adenocarcinoma within 12 cm from the anal verge with radiological evidence of perirectal fat or lymph node involvement. Randomization was between infused FU (225 mg/msq/day) concomitant to external-beam pelvic radiation (50.4 Gy in 28 daily fractions) (arm A) or the same regimen + weekly OXA (60 mg/msq x 6) (Arm B). Surgery was scheduled 6-8 weeks after completing CRT. Overall survival was the primary endpoint. A protocol-planned analysis of local tumor response to preop treatment (secondary end-point) is the object of this report. Results: 747 pts from 41 Italian centers were randomized between 12/2003 and 8/2008 (arm A/B: 379/368). Pretreatment characteristics in arm A/B: median age 63/62 years; male:female 2:1; median distance from anal verge 6 cm; T4 16/14%, N+ 63/65%. Overall grade 3-4 toxicity rates on treated pts (mainly diarrhoea) were 8% and 24% (arm A/B, p<0.001). 96/90% of pts (arm A/B) received > 90% of the planned RT. 82% of Arm B pts had > 5 oxa courses. 358/342 pts (arm A/B) had surgery at a median of 52/53 days from the end of CRT , 14 pts in each arm were not operated (progression 8, death 5, other/unknown 15) and surgery data are not yet available for 19 pts. Pathologic response data analyzed on the randomized population are reported in the table. Conclusions: The addition of weekly OXA to standard FU-based preop CRT significantly increases toxicity without affecting local tumor response. The reduced pathologic M+ rate suggests a potential effect on distant micrometastases. Longer follow-up is needed to assess the impact on efficacy endpoints.
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Direttore responsabile Mauro Boldrini