- Email: [email protected]
II TRIAL OF PANITUMUMAB, CAPECITABINE AND 3D-CRT AS PREOPERATIVE TREATMENT IN RECTAL CANCER
ESTRO 31
patients were under70yr and 52 over70yr: the KPS of the entire group was >60%. All these patients were accrued in several phase II studies, published on peer reviewed journals since 1998 to 2006. In the group of elderly patients the mean age was 74 years, in the under70yr was 59yr; the two groups were similar in terms of site of disease and stage: the most tumours were very low located, the stage at diagnoses varied from cT2N1M0, cT3N0-2 to cT4 (only with vagina infiltration)N0M0. The CRT protocol varied according to the period of accrual: the total dose of radiotherapy was 50 Gy (45-55Gy) with onetwo drugs chemotherapy (5fu +/-mitomycin/cisplatin, capecitabine +/- oxaliplatin). In the over70yr and in the under70yr groups, the rate of radical surgery were 63,5% and 68,5%, respectively (p=0,308): there was an higher rate of local excision in the first group, mainly due to coexisting comorbidities. The sphincter saving surgery was overlapped: 86,5%vs 81,7% (p=0,412); the pathologic response was similar in the two groups. Acute and late toxicity, perioperative morbidity and postoperative mortality were not significantly different. The median follow-up was 62 months (24-169): the 5yr-local control were 85,9% vs 84% (p=0,8), the 5yr-disease free survival were 73,7% vs 72,8% (p=0,9) and 5yr-overall survival were 75,9% vs 79,8% (p=0,48) in the over70yr and under70yr group, respectively. Conclusions: preoperative long course radio-chemotherapy in elderly patients status is a well tolerated treatment with promising long term outcomes: the accurate selection at the beginning of treatment is a valid strategy. EP-1073 PHASE I/II TRIAL OF PANITUMUMAB, CAPECITABINE AND 3D-CRT AS PREOPERATIVE TREATMENT IN RECTAL CANCER A. Varveris1, M. Mazonakis2, J. Stratakis2, A. Dimopoulos3, N. Trogkanis1, P. Sakarelis1, S. Stylianidou4, P. Pistevou4, C. Varveris1 1Heraklion University Hospital, Department of Radiotherapy & Oncology, Heraklion Crete, Greece 2Heraklion University Hospital, Department of Medical Physics, Heraklion Crete, Greece 3Metropolitan Hospital, Department of Radiotherapy & Oncology, Piraeus, Greece 4Achepa University Hospital, Department of Radiotherapy & Oncology, Thessaloniki, Greece Purpose/Objective: To evaluate the safety and activity (the pCR rate) of preoperative external external 3D- Conformal Radiotherapy (3DCRT) with concurrent Capecitabine and Panitumumab in locally advanced rectal cancer patients. Materials and Methods: 15 patients with histologically confirmed staged T2-4 NO-2MO adenocarcinoma of the rectum were included. Positive EGFR staining with no K-ras mutations was required and a total radiation dose of 5040cGy in 28 daily fractions of 1.8Gy (3 to 4 field technique, 5d/wk) with 3D-CRT and 18MV Photons. Capecitabine at a dose of 1600mg/m2/d was given every day for 5.6 weeks total treatment time. Panitumumab (3mg/kg.i.v) was delivered weekly during RT and then after RT at 6mg/kg every 2 weeks for 4 times until Surgery. One more cycle of Capecitabine was given at week 4 and 5 for 14 days after RT. Resection was performed 8 weeks after concurrent chemoradiation (CCRT) completion. Results: The primary end point was pCR (pathologic Complete Response): (Absence of viable tumor in the primary tumor/lymph nodes). A pPR was defined as >50% tumor mass regression in the pathology specimen. A pCR was observed in 2 patients (13.4%) while a pPR in 11 (73.3%). Two patients refused surgery and they were treated with a boost 3D-CRT to a total of 75.60cGy. One of those received in addition an interstitial implant (1.6Gy) in 2 fractions, a week apart. All patients received postoperative adjuvant chemotherapy with Capecitabine and Oxaliplatin: The most common side effects included Grade 1/2 and 3 acneiforn rash in 5 (33%), 1 (7%) patients respectively and Grade 3 diarrhea in 4 (26%) patients. Sphincter preserving surgery was accomplished in 2/5 patients for whom abdominoperineal resection was planned before CCRT. Conclusions: Upfront Panitumumab monotherarpy after CCRT completion with Capecitabine per os and panitumumab iv on a weekly basis, is feasible and well tolerated. The preliminary efficacy is very promising. Larger phase II trials are required. EP-1074 HELICAL TOMOTHERAPY IN THE TREATMENT OF ANAL CANCER: THE LAUSANNE EXPERIENCE H. Bouchaab1, O. Matzinger1, P. Tsoustou1, S. Peters2, M. Pachoud1, R.O. Mirimanoff1, M. Ozsahin1
S417
1
Centre Hospitalier Univ. Vaudois, radio oncologie, Lausanne, Switzerland Centre Hospitalier Univ. Vaudois, oncologie, Lausanne, Switzerland
2
Purpose/Objective: To report a single-center experience treating patients with squamous –cell carcinoma of the anal canal using helical tomotherapy (HT) and concurrent chemotherapy. Materials and Methods: From October 2007 to February 2011, 54 patients were treated with HT and concurrent chemotherapy (5fluorouracil /capecitabin and mitomycin) for anal squamous-cell carcinoma. All patients underwent computed-tomography-based treatment planning, with pelvic regions and inguinal nodes receiving 36 Gy in 1.8 Gy per fraction. Following a planned one-week break, primary tumor site and involved nodes were boosted to a total dose of 59.4 Gy. Dose-volume histograms of several organs at risk (OAR; bladder, small intestin, rectum, femoral heads, penile bulb, external genitalia) were assessed in terms of conformal avoidance. All toxicity was scored according to the CTCAE, v.3.0. Locoregional control and survival curves were compared with the long-rank test, and multivariate analysis by the Cox model Results: At a median follow-up of 36 months, overal survival rate was 88%, the disease-free survival rate was 76%, and local control rate was 88%. Acute grade 3 dermatitis, diarrhea, and proctitis occured in 12 patients (22%).At last follow-up, late grade1 anal-incontinence was documented in only 4 patients. A temporary colostomy was implemented in 2 patients, and definitive colostomy as salvage treatment was performed in 3 patients. Conclusions: Organ preservation treatment using helical tomotherapy and concurrent chemotherapy is well tolerated. Our results are encouraging with a good local control and acceptable toxicity (colostomy rate =5/54, 9%; disease-related colostomy rate =3/54,6%). EP-1075 PRIMARY CONFORMAL RADIOTHERAPY AND CHEMOTHERAPY FOR ESOPHAGEAL CANCER: PRELIMINARY RESULTS OF A RANDOMIZED TRIAL M. Ibraimova1, V. Kim1, T. Antropova1, R. Abdrakhmanov1, A. Almabek1, Y. Ishkinin1, O. Truschenko1, Y. Malysheva1 1 Kazakh research institute of oncology and radiology, Academic Physics, Almaty, Kazakhstan Purpose/Objective: To compare treatment outcome of two chemoradiotherapy regimen for esophageal cancer. Materials and Methods: Between September 2006 and September 2011, 76 patients (45 men (59.2%) and 31 women (40.8%), age range 53-74, median 63.5 year) were enrolled. Tumor of all patients was located in the thoracic region of the esophagus. In all cases, was a squamous cell carcinoma histology form. All patients initially were conducted four courses of chemotherapy according to the scheme: gemcitabine 1000 mg/m² at 1 and 8th days, cisplatin 75 mg/m² in 1-day. Interval between courses of chemotherapy was 21 days. For the radiotherapy was used a high dose rate 6- MV beam from a Varian Clinac 600 linear accelerator with 3D planning system Eclipse. Then, patients were divided 2 groups according of the radiotherapy method. For first group – included 39 (51.3%) patients, was perfumed conformal radiotherapy at 2.0 Gy per fraction (#35) to a total dose 70 Gy. Second group included 37 (48.7%) patients, was perfumed conventional radiation therapy at 2.0 Gy per fraction (#30) to a total dose 60 Gy, for 2 or 3 static mode fields. In both groups, radiation therapy was carried out together with chemotherapy (5 or 6 courses). Results: The overall objective effect after treatment was achieved for first group - 35 patients (89.7%) and for second group 23 patients (62.1%). Complete tumor regression was achieved for first group - 15 patients (38.5%) and 6 (16.2%) patients for second group. During the treatment of hematologic manifestations and gastrointestinal toxicity grade IV was not observed. Radiation esophagitis was observed on 37 (94.8%) and 36 (97.2%) patients of the 1st and 2nd groups, respectively. We not observed radiation reactions and any complications from heart and lung system for patients receiving conformal radiation therapy. For second group, those reactions were observed on 12 patients (32.4%). Conclusions: Thus, the preliminary results of clinical studies demonstrated the effectiveness of the proposed regime of chemotherapy and its combination with conformal radiation therapy is not related with increase of the limiting toxicity.
patients were under70yr and 52 over70yr: the KPS of the entire group was >60%. All these patients were accrued in several phase II studies, published on peer reviewed journals since 1998 to 2006. In the group of elderly patients the mean age was 74 years, in the under70yr was 59yr; the two groups were similar in terms of site of disease and stage: the most tumours were very low located, the stage at diagnoses varied from cT2N1M0, cT3N0-2 to cT4 (only with vagina infiltration)N0M0. The CRT protocol varied according to the period of accrual: the total dose of radiotherapy was 50 Gy (45-55Gy) with onetwo drugs chemotherapy (5fu +/-mitomycin/cisplatin, capecitabine +/- oxaliplatin). In the over70yr and in the under70yr groups, the rate of radical surgery were 63,5% and 68,5%, respectively (p=0,308): there was an higher rate of local excision in the first group, mainly due to coexisting comorbidities. The sphincter saving surgery was overlapped: 86,5%vs 81,7% (p=0,412); the pathologic response was similar in the two groups. Acute and late toxicity, perioperative morbidity and postoperative mortality were not significantly different. The median follow-up was 62 months (24-169): the 5yr-local control were 85,9% vs 84% (p=0,8), the 5yr-disease free survival were 73,7% vs 72,8% (p=0,9) and 5yr-overall survival were 75,9% vs 79,8% (p=0,48) in the over70yr and under70yr group, respectively. Conclusions: preoperative long course radio-chemotherapy in elderly patients status is a well tolerated treatment with promising long term outcomes: the accurate selection at the beginning of treatment is a valid strategy. EP-1073 PHASE I/II TRIAL OF PANITUMUMAB, CAPECITABINE AND 3D-CRT AS PREOPERATIVE TREATMENT IN RECTAL CANCER A. Varveris1, M. Mazonakis2, J. Stratakis2, A. Dimopoulos3, N. Trogkanis1, P. Sakarelis1, S. Stylianidou4, P. Pistevou4, C. Varveris1 1Heraklion University Hospital, Department of Radiotherapy & Oncology, Heraklion Crete, Greece 2Heraklion University Hospital, Department of Medical Physics, Heraklion Crete, Greece 3Metropolitan Hospital, Department of Radiotherapy & Oncology, Piraeus, Greece 4Achepa University Hospital, Department of Radiotherapy & Oncology, Thessaloniki, Greece Purpose/Objective: To evaluate the safety and activity (the pCR rate) of preoperative external external 3D- Conformal Radiotherapy (3DCRT) with concurrent Capecitabine and Panitumumab in locally advanced rectal cancer patients. Materials and Methods: 15 patients with histologically confirmed staged T2-4 NO-2MO adenocarcinoma of the rectum were included. Positive EGFR staining with no K-ras mutations was required and a total radiation dose of 5040cGy in 28 daily fractions of 1.8Gy (3 to 4 field technique, 5d/wk) with 3D-CRT and 18MV Photons. Capecitabine at a dose of 1600mg/m2/d was given every day for 5.6 weeks total treatment time. Panitumumab (3mg/kg.i.v) was delivered weekly during RT and then after RT at 6mg/kg every 2 weeks for 4 times until Surgery. One more cycle of Capecitabine was given at week 4 and 5 for 14 days after RT. Resection was performed 8 weeks after concurrent chemoradiation (CCRT) completion. Results: The primary end point was pCR (pathologic Complete Response): (Absence of viable tumor in the primary tumor/lymph nodes). A pPR was defined as >50% tumor mass regression in the pathology specimen. A pCR was observed in 2 patients (13.4%) while a pPR in 11 (73.3%). Two patients refused surgery and they were treated with a boost 3D-CRT to a total of 75.60cGy. One of those received in addition an interstitial implant (1.6Gy) in 2 fractions, a week apart. All patients received postoperative adjuvant chemotherapy with Capecitabine and Oxaliplatin: The most common side effects included Grade 1/2 and 3 acneiforn rash in 5 (33%), 1 (7%) patients respectively and Grade 3 diarrhea in 4 (26%) patients. Sphincter preserving surgery was accomplished in 2/5 patients for whom abdominoperineal resection was planned before CCRT. Conclusions: Upfront Panitumumab monotherarpy after CCRT completion with Capecitabine per os and panitumumab iv on a weekly basis, is feasible and well tolerated. The preliminary efficacy is very promising. Larger phase II trials are required. EP-1074 HELICAL TOMOTHERAPY IN THE TREATMENT OF ANAL CANCER: THE LAUSANNE EXPERIENCE H. Bouchaab1, O. Matzinger1, P. Tsoustou1, S. Peters2, M. Pachoud1, R.O. Mirimanoff1, M. Ozsahin1
S417
1
Centre Hospitalier Univ. Vaudois, radio oncologie, Lausanne, Switzerland Centre Hospitalier Univ. Vaudois, oncologie, Lausanne, Switzerland
2
Purpose/Objective: To report a single-center experience treating patients with squamous –cell carcinoma of the anal canal using helical tomotherapy (HT) and concurrent chemotherapy. Materials and Methods: From October 2007 to February 2011, 54 patients were treated with HT and concurrent chemotherapy (5fluorouracil /capecitabin and mitomycin) for anal squamous-cell carcinoma. All patients underwent computed-tomography-based treatment planning, with pelvic regions and inguinal nodes receiving 36 Gy in 1.8 Gy per fraction. Following a planned one-week break, primary tumor site and involved nodes were boosted to a total dose of 59.4 Gy. Dose-volume histograms of several organs at risk (OAR; bladder, small intestin, rectum, femoral heads, penile bulb, external genitalia) were assessed in terms of conformal avoidance. All toxicity was scored according to the CTCAE, v.3.0. Locoregional control and survival curves were compared with the long-rank test, and multivariate analysis by the Cox model Results: At a median follow-up of 36 months, overal survival rate was 88%, the disease-free survival rate was 76%, and local control rate was 88%. Acute grade 3 dermatitis, diarrhea, and proctitis occured in 12 patients (22%).At last follow-up, late grade1 anal-incontinence was documented in only 4 patients. A temporary colostomy was implemented in 2 patients, and definitive colostomy as salvage treatment was performed in 3 patients. Conclusions: Organ preservation treatment using helical tomotherapy and concurrent chemotherapy is well tolerated. Our results are encouraging with a good local control and acceptable toxicity (colostomy rate =5/54, 9%; disease-related colostomy rate =3/54,6%). EP-1075 PRIMARY CONFORMAL RADIOTHERAPY AND CHEMOTHERAPY FOR ESOPHAGEAL CANCER: PRELIMINARY RESULTS OF A RANDOMIZED TRIAL M. Ibraimova1, V. Kim1, T. Antropova1, R. Abdrakhmanov1, A. Almabek1, Y. Ishkinin1, O. Truschenko1, Y. Malysheva1 1 Kazakh research institute of oncology and radiology, Academic Physics, Almaty, Kazakhstan Purpose/Objective: To compare treatment outcome of two chemoradiotherapy regimen for esophageal cancer. Materials and Methods: Between September 2006 and September 2011, 76 patients (45 men (59.2%) and 31 women (40.8%), age range 53-74, median 63.5 year) were enrolled. Tumor of all patients was located in the thoracic region of the esophagus. In all cases, was a squamous cell carcinoma histology form. All patients initially were conducted four courses of chemotherapy according to the scheme: gemcitabine 1000 mg/m² at 1 and 8th days, cisplatin 75 mg/m² in 1-day. Interval between courses of chemotherapy was 21 days. For the radiotherapy was used a high dose rate 6- MV beam from a Varian Clinac 600 linear accelerator with 3D planning system Eclipse. Then, patients were divided 2 groups according of the radiotherapy method. For first group – included 39 (51.3%) patients, was perfumed conformal radiotherapy at 2.0 Gy per fraction (#35) to a total dose 70 Gy. Second group included 37 (48.7%) patients, was perfumed conventional radiation therapy at 2.0 Gy per fraction (#30) to a total dose 60 Gy, for 2 or 3 static mode fields. In both groups, radiation therapy was carried out together with chemotherapy (5 or 6 courses). Results: The overall objective effect after treatment was achieved for first group - 35 patients (89.7%) and for second group 23 patients (62.1%). Complete tumor regression was achieved for first group - 15 patients (38.5%) and 6 (16.2%) patients for second group. During the treatment of hematologic manifestations and gastrointestinal toxicity grade IV was not observed. Radiation esophagitis was observed on 37 (94.8%) and 36 (97.2%) patients of the 1st and 2nd groups, respectively. We not observed radiation reactions and any complications from heart and lung system for patients receiving conformal radiation therapy. For second group, those reactions were observed on 12 patients (32.4%). Conclusions: Thus, the preliminary results of clinical studies demonstrated the effectiveness of the proposed regime of chemotherapy and its combination with conformal radiation therapy is not related with increase of the limiting toxicity.