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1.
Sakakibara-Konishi J Oizumi S Kinoshita I Shinagawa N Kikuchi J Kato M Inoue T Katoh N Onimaru R Shirato H Dosaka-Akita H Nishimura M 《Lung cancer (Amsterdam, Netherlands)》2011,74(2):248-252
Introduction
Although paclitaxel with carboplatin and thoracic radiotherapy has improved survival for patients with locally advanced unresectable non-small cell lung cancer (NSCLC), the optimal dose of paclitaxel has not been well defined in Japan. This study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of paclitaxel in combination with carboplatin and concurrent real-time tumor-tracking thoracic radiation therapy (thoracic RTRT).Patients and methods
Previously untreated patients with histologically confirmed, locally advanced unresectable NSCLC were eligible. Before treatment, gold markers were inserted into the lung and the mediastinum of all patients. RTRT comprised a total of 66 Gy at 2 Gy/fraction, 5 days/week, for 7 weeks. Patients received paclitaxel at a starting dose of 40 mg/m2 followed by carboplatin at a fixed area under the curve (AUC) of 2, as a weekly regimen with RTRT. The dose of paclitaxel was escalated by 5 mg/m2 per level.Results
Eight patients with locally advanced unresectable NSCLC were enrolled and treated with two dose levels of paclitaxel (40 mg/m2 and 45 mg/m2), carboplatin (AUC = 2) and RTRT. No dose limiting toxicities (DLTs) were observed at Level 1 (paclitaxel, 40 mg/m2 and carboplatin, AUC = 2). At Level 2 (paclitaxel, 45 mg/m2 and carboplatin, AUC = 2), two of five patients experienced DLTs, in the form of esophagitis and discontinuation of chemotherapy more than twice. The MTD and RD of paclitaxel were thus defined as 45 mg/m2 and 40 mg/m2, respectively.Conclusions
This phase I study was well tolerated and the RD of paclitaxel and carboplatin with RTRT is 40 mg/m2 at AUC = 2, respectively. Further studies are warranted to evaluate the efficacy of this regimen. 相似文献2.
Han HS Reis IM Zhao W Kuroi K Toi M Suzuki E Syme R Chow L Yip AY Glück S 《European journal of cancer (Oxford, England : 1990)》2011,47(17):2537-2545
Background
Racial disparities in breast cancer outcomes are attributed to differences in baseline tumour characteristics and biology, stage, age, ethnic background and socioeconomic factors. However, little is known about racial differences in treatment-related toxicities. We hypothesised that racial/ethnic differences result in differential tolerance to chemotherapy potentially, leading to compromised dose intensity/density of chemotherapy in patients with early-stage breast cancer.Methods
Data were collected from patients treated at five international centers for early breast cancer with the same adjuvant/neoadjuvant chemotherapy (FEC 100: fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2,every 21 d for 3-6 cycles). Toxicities were assessed by first episode of ?grade 2 toxicity.Results
Toxicities were compared according to four race/ethnicity groups (103 Caucasian, 30 African American, 164 Asian, and 34 Hispanic patients). Tumour characteristics across four race/ethnicity groups were similar. Asians had a significantly higher rate of grade 3 haematologic toxicity than Caucasians, African Americans or Hispanic women (32%, 16%, 10%, and 15%, respectively; p < 0.05). In multivariate analysis, only lower BMI was associated with a higher incidence of ?grade 3 toxicities. However, no significant differences in chemotherapy dose intensity/density were shown across the four race/ethnicity groups.Conclusion
Racial differences in acute toxicity were noted in women with breast cancer who were treated with FEC 100 chemotherapy, suggesting that extrapolating toxicities from chemotherapy across ethnicities is not possible and emphasising the need to validate safety of chemotherapeutic regimens in patients of different ethnicities by enhancing the participation of minorities in clinical trials. 相似文献3.
de Jonge MJ Dumez H Kitzen JJ Beuselinck B Verweij J Courtney R Battista A Brega N Schöffski P 《European journal of cancer (Oxford, England : 1990)》2011,47(9):1328-1335
Background
In pre-clinical models enhanced anti-tumour activity was observed when SU-014813, an oral multi-targeted tyrosine kinase inhibitor was combined with docetaxel. This synergy might be explained by improvement of the penetration of cytotoxic agents into tumours as a result of both VEGFR and PDGFR inhibition. We assessed the maximal tolerated dose (MTD), evaluated the pharmacokinetics and preliminary anti-tumour efficacy of oral SU-014813 administered continuously in combination with docetaxel to patients with advanced solid tumours.Methods
In this phase I study successive patient cohorts received docetaxel 60 or 75 mg/m2 every 3 weeks in combination with chronic daily dosing of SU-014813. Dose limiting toxicity was assessed both in the first and second treatment cycle.Results
Twenty-five patients were entered on study of which 24 started treatment. Dose limiting toxicities were prolonged neutropenia, neutropenic fever, fatigue and diarrhoea. Other toxicities included fatigue, alopecia, nausea, vomiting, anorexia, rash, hypertension and hair discolouration. The recommended phase II dose was determined to be docetaxel 75 mg/m2 in combination with SU-014813 50 mg/day. There was no clinically relevant pharmacokinetic drug-drug interaction. Two patients (8%) achieved a partial response (PR) and 7 patients (29%) had stabilisation of their disease (SD) >6 months, for a clinical benefit rate of 37.5%. The activity observed in patients with melanoma and sunitinib refractory gastrointestinal stromal tumours (GIST) was particularly noteworthy.Conclusions
Oral SU-014813 50 mg/day with docetaxel 75 mg/m2 is a clinically feasible regimen with a manageable safety profile and anti-tumour activity. Further development is warranted in patients with melanoma and GIST. 相似文献4.
Cohen EE Sharma MR Janisch L Llobrera M House L Wu K Ramirez J Fleming GF Stadler WM Ratain MJ 《European journal of cancer (Oxford, England : 1990)》2011,47(10):1484-1489
Background
We performed a single institution, phase I study of sirolimus and bevacizumab, in order to determine the dose limiting toxicity (DLT) and recommended phase II doses.Patients and methods
Eligible patients had previously treated advanced malignancies and were enrolled in three cohorts. Sirolimus 90 mg PO weekly (45 mg on days 1 and 2) was combined with bevacizumab 7.5 mg/kg (cohort #1) or bevacizumab 15 mg/kg (cohort #2) IV q3weeks. Sirolimus 4 mg PO daily was combined with bevacizumab 15 mg/kg IV q3weeks (cohort #3).Results
Twenty-eight patients enrolled. The most common tumour types were colorectal (21%), head/neck (14%), and renal cell (11%). No DLTs were observed in cohorts #1 (4 patients) and #2 (12 patients), while two DLTs (grade 3 confusion and grade 3 fatigue) were observed in the first six patients in cohort #3 (12 patients). The most common grade 3 toxicities were fatigue (18%), hypertension (14%) and anorexia (11%). There were no responses, but one patient has had stable disease for 78 weeks.Conclusions
The combination of sirolimus and bevacizumab at full doses is tolerable in the majority of patients. The availability and cost of sirolimus compared with other mTOR inhibitors make this an attractive agent to combine with bevacizumab. 相似文献5.
Adalsteinn Gunnlaugsson Harald Anderson Bengt Glimelius Anders Johnsson 《Radiotherapy and oncology》2010,95(3):292-297
Background and Purpose
In this multicentre phase I-II trial we evaluated the feasibility and efficacy of capecitabine and oxaliplatin followed by the combination of these two drugs with radiotherapy in patients with locally advanced pancreatic or biliary tract cancer.Material and methods
Thirty-nine patients with inextirpable adenocarcinoma of the pancreas, gallbladder or extrahepatic bile ducts were included. Two cycles of XELOX (capecitabine 1000 mg/m2 bid d1-14 + oxaliplatin 130 mg/m2 d1, q3w) were followed by XELOX-RT (radiotherapy (50.4 Gy), combined with capecitabine 750-675 mg/m2 bid every radiotherapy day and oxaliplatin 40-30 mg/m2 once weekly). Primary end-points were tolerance (phase I) and objective response (phase II).Results
The maximum tolerated doses of oxaliplatin and capecitabine to combine with irradiation were 30 mg/m2 and 675 mg/m2, respectively. Twenty-one percent (95% CI: 9-38%) of evaluable patients achieved partial response. Five patients went through surgery (three R0 resections). Two-year survival was 28%, and estimated local tumour control rate at 2 years was 72%. The most common grade 3-4 toxicity was nausea and vomiting.Conclusions
XELOX-RT (30 mg/m2 oxaliplatin/675 mg/m2 capecitabine in combination with 50.4 Gy/28 fractions) was well tolerated and effective for locally advanced pancreatic and biliary tract cancer. 相似文献6.
S. Agelaki E. Kontopodis A. Kotsakis V. Chandrinos I. Bompolaki Ζ. Zafeiriou E. Papadimitraki D. Stoltidis K. Kalbakis V. Georgoulias 《Cancer chemotherapy and pharmacology》2013,72(1):45-51
Purpose
To determine the dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of oral topotecan administered weekly in patients with relapsed small cell lung cancer (SCLC).Patients and methods
Patients were treated with oral topotecan on days 1, 8, and 15, every 28 days. The dose was escalated by 0.5 mg/m2 increments from the starting dose of 3 mg/m2 until the MTD was reached. DLTs were defined as grade 4 neutropenia, febrile neutropenia, grade 4 thrombocytopenia, non-hematologic toxicity ≥grade 3, any toxicity precluding the treatment on days 8 or 15 of the first cycle, or delay of the second cycle for more than 7 days.Results
Eighteen patients were enrolled. Thirteen patients received oral topotecan as second-line and five as third- or further-line treatment. The DLT level was reached at 4.5 mg/m2, and the MTD was determined to be 4 mg/m2. DLTs consisted of grade 2/3 neutropenia and grade 2 thrombocytopenia precluding treatment on day 15 of the first cycle or on day 1 of the second cycle. The most frequent toxicities were grade 2–3 neutropenia (27.8 % of patients), grade 2–3 anemia (33.3 %), grade 2 thrombocytopenia (16.7 %), and grade 2–3 fatigue (44.4 %). The response rate was 11.1 %, the median progression-free survival 2.3 months, and the median overall survival 5.1 months.Conclusion
The recommended phase II dose of weekly oral topotecan in pretreated patients with SCLC is 4 mg/m2 on days 1, 8, and 15 every 28 days. 相似文献7.
Califano R Griffiths R Lorigan P Ashcroft L Taylor P Burt P Lee L Chittalia A Harris M Faivre-Finn C Thatcher N Blackhall F 《Lung cancer (Amsterdam, Netherlands)》2011,73(3):338-344
Background
The role of chemotherapy for advanced NSCLC patients and ECOG PS2 remains controversial. We evaluated 4 doses of 3-weekly docetaxel to identify a less toxic, clinically effective dose.Methods
Seventy-three patients with stage III (22%) (unsuitable for radical surgery/radiotherapy) and IV (78%) NSCLC were randomized to receive 4 doses of 3-weekly docetaxel, for 4 cycles: arm (A) 40 mg/m2 (n = 17), arm (B) 50 mg/m2 (n = 17), arm (C) 60 mg/m2 (n = 19), arm (D) 50 mg/m2 escalated by 10 mg/m2 to a maximum of 70 mg/m2 (n = 19). Primary endpoints: maximum tolerated dose, RR, duration of response, symptom improvement, toxicity and QoL. Secondary endpoint: overall survival (OS). Patients and disease characteristics were well balanced. Median age was 67 (range 45-81), there were 32 male and 41 female, histology subtype: squamous/adenocarcinoma/mixed/NOS = 42%/49%/4%/5%.Results
Seven patients did not receive any treatment because of deterioration in PS or death. 50% of patients in arm D, who received more than one cycle, received dose escalation. There was no statistical difference in the number of cycles administered (arms A, B and D: median 2 cycles and arm C: median 3 cycles) and no difference in RR: arm A = 6%, arm B = 6%, arm C = 10%, and arm D = 0%. There was no statistically significant difference in grade 3/4 neutropenia and thrombocytopenia between the four arms. No difference was observed in hospitalization rate, blood transfusions, antibiotics administration and non-haematological toxicity. QoL: no difference in total scores between baseline and cycles 1-4. There was a significant decrease in pain scores from baseline to post cycles 2 and 3 (p = 0.025 and p = 0.002, respectively). There was no difference in OS (p = 0.992). Median survival and 6-month survival were 61, 86, 88 and 97 days and 29%, 33%, 21% and 26% for arms A, B, C, and D, respectively.Conclusions
Clinical efficacy of docetaxel was observed at all dose levels. Higher dose levels were not associated with increased toxicities, use of IV antibiotics or hospitalization rates. However, the median survival observed is shorter than historical data and do not support further evaluation of these doses of single agent docetaxel in this population. 相似文献8.
Belvedere O Follador A Rossetto C Merlo V Defferrari C Sibau AM Aita M Dal Bello MG Meduri S Gaiardo M Fasola G Grossi F 《European journal of cancer (Oxford, England : 1990)》2011,47(11):1653-1659
Introduction
To date, no combination regimen has proven superior to single agent chemotherapy as a second-line treatment for non-small cell lung cancer (NSCLC).Methods
This multicenter, non-comparative randomised phase II trial evaluated the activity of docetaxel (75 mg/m2 on day 1) with oxaliplatin (70 mg/m2 on day 2) every 3 weeks in previously treated NSCLC patients; the reference arm was single-agent docetaxel (75 mg/m2 on day 1 every 3 weeks). It was designed as a one-stage, three-outcome phase II trial; 21 evaluable patients were required in each arm. The primary end-point was response rate; secondary end-points were toxicity, progression free survival (PFS) and overall survival.Results
Fifty patients were enrolled. Patient characteristics included male/female, 76/24%; median age 62 years; ECOG PS 0/1, 36/64%; previous platinum-based chemotherapy, 98%. Partial response was seen in 20% and 8%, stable disease in 52% and 32%, of patients treated with docetaxel/oxaliplatin and docetaxel, respectively. Main grade 3-4 toxicities were neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhoea 12% and 4% for docetaxel/oxaliplatin and docetaxel, respectively. Median PFS was 5.0 and 1.7 months, median survival 11.0 and 7.1 months, and 1-year survival 44% and 32% for docetaxel/oxaliplatin and docetaxel, respectively.Conclusions
The study met its pre-defined study end-point; docetaxel/oxaliplatin and more generally platinum-containing doublets warrant further evaluation as second-line therapy for patients with NSCLC. 相似文献9.
Wei Hu Weijun Ding Minghai Shao Jianhua Wang Shixiu Wu Charlie C.-M. Ma 《Radiotherapy and oncology》2009,93(3):488-491
Purpose
To evaluate the efficacy and toxicity of weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy (AC) in patients with locally advanced nasopharyngeal carcinoma (NPC).Methods and materials
Between 2004 and 2007, 54 patients with locally advanced NPC were included in this protocol. Patient characteristics: median age 48; 69% male; 52% World Health Organization (WHO) III; 50% stage III, 50% stage IV. The patients underwent a course of definitive conventional radiotherapy (70 Gy in 7 weeks with 2 Gy/fraction), with concurrent weekly paclitaxel 35 mg/m2 from the first to the sixth week of radiation. AC was started 4 weeks after the end of the radiotherapy (RT), paclitaxel 135 mg/m2 on day 1 and cisplatin 30 mg/m2 on days 1-3 were administered every 4 weeks for two cycles.Results
Median follow-up was 32 months. Eighty-five percentage of complete response and 15% partial response were achieved at the time of one month after AC. The 3-year actuarial rate of local regional control was 86%; distant metastases-free survival, progression-free survival and overall survival at 3 years were 81%, 69% and 76%, respectively. Forty-nine (91%) patients completed six courses of concurrent chemotherapy with weekly paclitaxel, and 4 (7%) patients delayed at the second cycle of AC. No patient developed severe acute toxicities.Conclusions
Weekly paclitaxel with concurrent RT followed by AC is a potentially effective and toxicity tolerable method for locally advanced NPC. Further studies are needed to identify the optimal dose of weekly paclitaxel in this strategy. 相似文献10.
Annemarie T. Swaak-Kragten Johannes H.W. de Wilt Marijke Bontenbal 《Radiotherapy and oncology》2009,92(1):100-104
Purpose
To retrospectively analyze the outcome of patients with anaplastic thyroid carcinoma (ATC) treated in the Erasmus MC.Material and methods
Seventy-five ATC-patients were treated between 1972 and 2003. Mean age was 68 years. Tumor stage was IVA in 9%, IVB in 51%, and IVC in 40%. Thirty-six patients underwent up-front surgery, with 53% resulting in R0/R1 resection. Before 1988 adjuvant treatment consisted of conventional radiotherapy (RT) and/or chemotherapy (CT). As of 1988, 30 eligible patients were enrolled in a newly designed protocol. This consists of locoregional RT in 46 fractions of 1.1 Gy, given twice daily, followed by prophylactic irradiation of the lungs (PLI) in 5 daily fractions of 1.5 Gy. During radiation, low-dose Doxorubicine (15 mg/m2) is administered weekly and is followed by adjuvant Doxorubicine (50 mg/m2) 3-weekly up to a cumulative dose of 550 mg/m2. Twenty-five ineligible patients were treated conventionally.Results
Overall median survival was 3 months, 1-year OS 9%. Locoregional control was significantly higher in patients who had undergone R0/R1 resection or chemoradiation, with best results for patients who underwent both (complete remission in 89%). However, the survival benefit of patients who reached CR remained borderline (median OS 7 months, 1-year OS 32%). Three patients survived for more than 5 years; all had undergone R0/R1 surgical resection and chemoradiation. Acute toxicity in the protocol group was significantly higher than in the nonprotocol group, with 46% versus 11% grade 3 pharyngeal and/or esophageal toxicity.Conclusion
Despite the ultimately dismal prognosis of ATC-patients, multimodality treatment significantly improved local control and improved the median survival. 相似文献11.
目的 探讨局部不可手术或局部复发直肠癌常规3个野等中心照射或三维适形放疗同步羟基喜树碱的剂量限制性不良反应(DLT)和最大耐受剂量。方法 2004—2007年间 22例局部不可手术或局部复发直肠癌患者入组研究。按照羟基喜树碱(HCPT)用法分为1 次/周用药组和2 次/周用药组,剂量分别为6、8、10 mg/m2和4、6、8、10 mg/m2,从放疗开始同步经静脉注射。盆腔常规分割,总剂量50 Gy,局部肿瘤部位序贯加量 10~16 Gy。≥3级非血液学和4级血液学不良反应为HCPT的DLT。结果 2 次/周用药组 8例患者完成了2个水平剂量递增试验,其中4 mg/m2组未出现DLT,6 mg/m2组前 3例出现 1例DLT (3级腹泻)、追加 3例后再次出现 1例DLT (3级腹泻)。1 次/周用药组 14例患者完成了3个水平剂量递增试验,其中6 mg/m2组未出现DLT,8 mg/m2组前 3例出现 1例DLT (3级腹泻、放射性皮炎)、追加 3例后未出现DLT,10 mg/m2出现 1例DLT (3级腹泻)、追加的第 2例出现DLT (3级恶心)。全组 5年总生存率为23%,中位生存期18个月。结论 局部不可手术或局部复发直肠癌放疗同步HCPT推荐每周8 mg/m2,可1次或分为2次给与。剂量限制性不良反应为3级腹泻、恶心和放射性皮炎。 相似文献
12.
De Ioris MA Castellano A Ilari I Garganese MC Natali G Inserra A De Vito R Ravà L De Pasquale MD Locatelli F Donfrancesco A Jenkner A 《European journal of cancer (Oxford, England : 1990)》2011,47(4):572-578
Purpose
Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma.Methods
Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6 mg/m2 and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria.Results
Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable.Conclusions
These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma. 相似文献13.
Asakuma M Yamamoto M Wada M Ryuge S Katono K Yokoba M Fukui T Takakura A Otani S Maki S Igawa S Yanaihara T Mitsufuji H Kubota M Katagiri M Sasaki J Masuda N 《Cancer chemotherapy and pharmacology》2012,69(6):1529-1536
Purpose
We conducted a phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with amrubicin, a topoisomerase II inhibitor, with recombinant human granulocyte colony-stimulating factor (rhG-CSF) support to overcome the neutropenia associated with this particular combination. The aim was to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed dose of CPT-11 and the dose-limiting toxicities (DLTs) of this combination in extensive-stage small-cell lung cancer (ED-SCLC) patients.Methods
Fifteen patients with ED-SCLC were treated at 3-week intervals with amrubicin on days 1–3 plus 60?mg/m2 CPT-11 on days 1 and 8. In addition, prophylactic rhG-CSF (50?μg/m2) was given from day 4 to day 21, except on the day of CPT-11 administration. Amrubicin was started at 30?mg/m2 and then escalated in 5?mg/m2 increments until MTD was reached.Results
The MTD of amrubicin was 35?mg/m2, since 2 of 4 patients experienced DLTs during the first cycle of treatment at the 40 mg/m2 dose level. Neutropenia, neutropenic fever, ileus, and diarrhea were the DLTs. There were 13 partial responses among the 13 assessable patients, yielding an overall response rate of 100?%. Median progression-free survival and overall survival were 7.4?months and 13.4?months, respectively.Conclusion
The combination of amrubicin and CPT-11 showed high activity against ED-SCLC with acceptable toxicity. Use of rhG-CSF allowed the dose of amrubicin to be raised 40?% above that in the original regimen (60?mg/m2 CPT-11 and 25?mg/m2 amrubicin). 相似文献14.
Jun Zhang Hiram A. Gay Suzanne Russo Teresa Parent Raid Aljumaily Paul R. Walker 《Lung cancer (Amsterdam, Netherlands)》2014
Objectives
The purpose of the proposed study is to evaluate the effectiveness and safety of low-dose paclitaxel with timed thoracic radiotherapy (TTR) for local control by inducing maximum radiosensitization through G2-M phase cell cycle arrest, followed by full dose adjuvant chemotherapy with gemcitabine and carboplatin for eradication of possible micrometastasis in unresectable stage III non-small cell lung cancer (NSCLC).Materials and methods
This is a single-center, non-randomized prospective phase II study. Patients with unresectable stage III NSCLC were treated with paclitaxel 15 mg/m2 IV, followed by TTR 6 h later on Monday/Wednesday/Friday, and TTR only on Tuesday/Thursday mornings (total 55 Gy). Full dose adjuvant chemotherapy consisted of intravenous carboplatin (AUC 5) on day 1, gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days for 4 cycles. The primary endpoint was overall survival (OS). Secondary endpoints were overall response rate (ORR), and toxicities.Results
Twenty-seven patients were eligible for the study. Patient characteristics were: 19 males (70%); median age 67 years (range 39–82); 15 (56%) stage IIIB; 89% with ECOG performance status ≥1. Three-year OS was 16.7% in all patients, and 27.3% in patients received three or more cycles of adjuvant chemotherapy, respectively. ORR was 63%. Grade 3 toxicities during paclitaxel plus concurrent TTR phase were radiation esophagitis (11%) and radiation pneumonitis (4%), no grade 4 toxicities occurred. One grade 5 hemoptysis. Grade 3/4 toxicities during adjuvant gemcitabine/carboplatin were pneumonitis (22%), anemia (30%), neutropenia (22%), and thrombocytopenia (33%), one grade 5 neutropenic fever.Conclusion
Low-dose paclitaxel with concurrent TTR is an effective chemoradiotherapy regimen in unresectable stage III NSCLC. Improved survival benefit was observed in patients who have received three or more cycles of full dose adjuvant chemotherapy, yet, gemcitabine related radiation pneumonitis and hematological toxicities limited adjuvant chemotherapy delivery. 相似文献15.
John H.L. Matthews Bryan H. BurmeisterMartin Borg Anne L. CappDavid Joseph Kerin M. ThompsonPaul I. Thompson Jennifer A. HarveyNigel A. Spry 《Radiotherapy and oncology》2011,98(1):93-98
Background and purpose
Elective inguinal irradiation increases morbidity. We describe outcomes of moderate intensity chemoradiation treating anal canal and adjacent pelvic nodes only.Material and methods
Forty patients with T1-2, N0 anal carcinoma were enrolled between March 1999 and March 2003. Inguinal nodes were NOT electively irradiated. The anal canal and regional pelvic nodes received 36 Gy/20# over 4 weeks, and 2 weeks later the anal canal was boosted with 14.4 Gy/8#. Chemotherapy was 5 fluorouracil 800 mg/m2/day on days 1-4 and 36-39, and Mitomycin C 10 mg/m2 on day 1.Results
Median follow-up was 44 months. Complete response was 95%. Four year results were; overall survival 71%, local control 82%, and colostomy-free survival (including salvage) 85%. Inguinal failure occurred in 22.5% but was isolated in only 12.5%. Treatment was well tolerated acutely with no toxic deaths. Severe late toxicity occurred in 7.5%.Conclusions
This moderate dose ‘non inguinal’ chemoradiation regimen resulted in modest acute toxicity, minimal long term morbidity and local control in line with other series. However staging failed to identify 12.5% of patients whose isolated inguinal failure might have been prevented by elective irradiation. Without more effective staging, all patients should receive elective inguinal irradiation. 相似文献16.
Amadori D Milandri C Comella G Saracchini S Salvagni S Barone C Bordonaro R Gebbia V Barbato A Serra P Gattuso D Nanni O Baconnet B Gasparini G 《European journal of cancer (Oxford, England : 1990)》2011,47(14):2091-2098
Aim
To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC).Patients and methods
The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6-8 cycles of Myocet® 50 mg/m2 (day 1), docetaxel 30 mg/m2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were assessed according to World Health Organisation criteria. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure and/or a decrease in left ventricular ejection fraction (LVEF).Results
The overall response rate was 55.6% (complete response 8.9%, partial response 46.7%), with a median time-to-progression of 10.9 months (C.I. 8.7-15.0). Median overall survival was not reached. The most frequent grade 3-4 adverse events were granulocytopaenia (60.0%), leukocytopenia (43.2%) and alopecia (35.6%). Grade 3-4 diarrhoea, pain, oral and skin toxicity (4.4%, each) and nausea/vomiting, thrombocytopenia and elevated alkaline phosphatase (2.2%, each) were also reported. In 2 patients LVEF fell to <50%, with a decrease from baseline >15%. LVEF median values remained stable from baseline to the end of the study (60%).Conclusions
The combination of Myocet®, docetaxel and trastuzumab is safe and shows promising activity as first-line treatment of HER-2-positive MBC. 相似文献17.
T. Yoshikawa K. Omura O. Kobayashi A. Nashimoto A. Takabayashi T. Yamada H. Yamaue M. Fujii T. Yamaguchi T. Nakajima 《European journal of surgical oncology》2010
Aims
Clinically serosa-positive (T3–4) gastric cancer has a poor prognosis. This phase II trial explored the feasibility and safety of preoperative chemotherapy followed by D2 or D3 gastrectomy in this type of gastric cancer.Methods
Patients with T3–4 gastric cancer received one course of S-1 (80 mg/m2 daily for 3 weeks) and cisplatin (60 mg/m2 on day 8) chemotherapy and then underwent D2 or D3 gastrectomy with curative intent. Primary endpoint was toxicities.Results
Of 50 patients enrolled, 49 were eligible and received the treatment protocol. Chemotherapy-related toxicities were mild; grade 3 neutropenia in 2 patients, anorexia in 3, and nausea in 2, and no grade 4 toxicities. Clinical response was achieved in 13 of 34 evaluable patients. Of the 49 patients, 39 underwent D2 or D3 dissection. There was no surgical mortality. Operative morbidity occurred in 5 of 49 patients, including pancreatic fistula in 1 and abdominal abscess in 2.Conclusion
This multi-modality treatment seems to be feasible and safe for T3–4 gastric cancer. 相似文献18.
Purpose
The antiangiogenic and immunomodulatory effects of thalidomide induce responses in patients with androgen-independent prostate cancer (AIPC). Paclitaxel and doxorubicin also have significant antitumor activity. A phase I dose-escalation study was conducted to evaluate the use of these agents in combination to enhance the chemotherapeutic effects of treatment for refractory cancer.Patients and Methods
Twelve men with AIPC (mean age, 64.5 years) and a median prostate-specific antigen (PSA) level of 30 ng/mL were enrolled. Patients received starting doses of weekly paclitaxel (100 mg/m2) as a 1-hour intravenous infusion, weekly doxorubicin (20 mg/m2) as a 24-hour intravenous infusion, and daily oral thalidomide at escalating dose levels of 200 mg (dose level 0), 300 mg (dose level +1), and 400 mg (dose level +2). Paclitaxel and doxorubicin were administered for 3 consecutive weeks of a 5-week cycle. Exposure to thalidomide was daily. Patients were evaluated weekly for dose-limiting toxicities to determine the maximum tolerated dose. In addition, PSA levels were measured before each cycle of treatment. Response to treatment was defined as a ≥ 50% decrease in baseline PSA levels associated with stable radiographic disease, improvement of bone scan results with plain radiograph correlation, or improvement in soft tissue disease.Results
Four patients were treated on dose level 0, 5 were treated on dose level +1, and 3 were treated on dose level +2. The thalidomide 400-mg dose level resulted in 3 of 3 patients experiencing grade 3 leukopenia. The maximum tolerated dose was 300 mg of thalidomide in combination with paclitaxel/doxorubicin. Nine of the 12 patients were evaluable for PSA response, with 88% exhibiting partial responses or stable disease. One patient (11%) had a significant response, with PSA levels decreasing > 90% from baseline values. Overall, PSA-level decreases ranged from 0.5 ng/mL to 39.5 ng/mL among the 9 evaluable patients. A maximum of 7 cycles of therapy were administered. Twelve patients were evaluable for toxicity: neutropenia (grade 3, 27%; grade 4, 54%), leukopenia (grade 3, 63%), constipation (grade 3, 27%), fatigue (grade 3, 27%), nausea (grade 3, 9%), and deep vein thrombosis (grade 3, 9%) were reported.Conclusion
The combined dosing of paclitaxel (100 mg/m2 weekly), doxorubicin (20 mg/m2 weekly), and thalidomide (300 mg daily) is tolerated by men with AIPC and merits continued phase II study. 相似文献19.
Marc A. BolletLisa Belin Fabien ReyalFrançois Campana Rémi DendaleYoulia M. Kirova Fabienne ThibaultVéronique Diéras Brigitte Sigal-ZafraniAlain Fourquet 《Radiotherapy and oncology》2012,102(1):82-88
Purpose
This phase II trial aimed to investigate the efficacy of concurrent radio- (RT) and chemotherapy (CT) in the preoperative setting for operable, non-metastatic breast cancer (BC) not amenable to initial breast-conserving surgery (BCS).Patients and methods
From 2001 to 2003, 59 women were included. CT consisted of four cycles of 5-FU, 500 mg/m2/d, continuous infusion (d1-d5) and vinorelbine, 25 mg/m2 (d1 and d6). Starting concurrently with the second cycle, RT delivered 50 Gy to the breast and 46 Gy to the internal mammary and supra/infra-clavicular areas. Breast surgery and lymph node dissection were then performed. Adjuvant treatment consisted of a 16 Gy boost to the tumor bed after BCS, FEC (four cycles of fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 100 mg/m2, d1; d21) for pN1-3 and hormone-therapy for positive hormone receptors BC.Results
The in-breast pathological complete response rate was 27%. BCS was performed in 41 (69%) pts. Overall and distant-disease free survivals at 5 years were respectively 88% [95% CI 80-98] and 83% [95% CI 74-93] whereas locoregional and local controls were 90% [95% CI 82-97] and 97% [95% CI 92-100]. Late toxicity (CTCAE-V3) was assessed in 51 pts (86%) with a median follow-up of 7 years [5-8]. Four (8%) experienced at least one grade III toxicities (one telangectasia and three fibroses). Cosmetic results, assessed in 35 of the 41 pts (85%) who retained their breasts, were poor in four pts (11%).Conclusion
Preoperative concurrent administration of RT and CT is an effective regimen. Long-term toxicity is moderate. This association deserves further evaluations in prospective trials. 相似文献20.
A. Hallqvist G. Wagenius H. Rylander O. Brodin E. HolmbergB. Lödén S.-B. Ewers S. BergströmG. Wichardt-Johansson K. NilssonL. Ekberg C. SederholmJ. Nyman 《Lung cancer (Amsterdam, Netherlands)》2011,71(2):166-172