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1.
A Roy D Cunningham R Hawkins H Sörbye A Adenis JR Barcelo G Lopez-Vivanco G Adler JL Canon F Lofts C Castanon E Fonseca O Rixe J Aparicio J Cassinello M Nicolson M Mousseau A Schalhorn L D'Hondt J Kerger DK Hossfeld C Garcia Giron R Rodriguez P Schoffski JL Misset 《British journal of cancer》2012,107(3):435-441
Background:
Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer.Methods:
Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m−2 plus irinotecan 250 mg m−2 (Day 1)) or 3-weekly DF (docetaxel 85 mg m−2 (Day 1) followed by 5-fluorouracil 750 mg m−2 per day as a continuous infusion (Days 1–5)).Results:
A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3–4 neutropenia, febrile neutropenia and diarrhoea were more frequent in the DI arm as compared with the DF arm (83.3% vs 69.8%, 40.5% vs 18.6%, and 42.9% vs 16.3%, respectively).Conclusion:
Both docetaxel-based doublet regimens show comparable efficacy; however, the DF regimen was associated with a better toxicity profile and is an alternative treatment option for patients in whom platinum-based regimens are unsuitable. 相似文献2.
S Sutherland S Ashley D Miles S Chan A Wardley N Davidson R Bhatti M Shehata H Nouras T Camburn S R D Johnston 《British journal of cancer》2010,102(6):995-1002
Background:
The global lapatinib expanded access programme provided access to lapatinib combined with capecitabine for women with HER2-positive metastatic breast cancer (MBC) who previously received anthracycline, taxane and trastuzumab.Methods:
Progression-free survival (PFS) and safety data for 356 patients recruited from the United Kingdom are reported. Efficacy was assessed in 162 patients from the five lead centres, including objective tumour response rate (ORR), time to disease progression (TTP) and efficacy in those with central nervous system (CNS) metastases. Correlation of PFS and ORR with previous capecitabine treatment was also documented.Results:
Overall, PFS for the 356 UK patients was 21 weeks (95% CI: 17.6–24.7). In the 162 assessable patients, ORR was 21% (95% CI: 15–27%) and median TTP was 22 weeks (95% CI: 17–27). Efficacy was greater in capecitabine-naive patients (ORR 23 vs 16.3%, P=0.008). For 34 patients with CNS metastases, ORR was 21% (95% CI: 9–39%), with evidence of improvement in neurological symptoms, and median TTP was 22 weeks (95% CI: 15–28).Conclusions:
Lapatinib combined with capecitabine is an active treatment option for women with refractory HER2-positive MBC, including those with progressive CNS disease. 相似文献3.
N C Tebbutt M M Cummins T Sourjina A Strickland G Van Hazel V Ganju D Gibbs M Stockler V Gebski J Zalcberg 《British journal of cancer》2010,102(3):475-481
Background:
Docetaxel administered 3-weekly with cisplatin and 5-fluorouracil leads to better survival than does standard therapy in patients with oesophagogastric cancer, but leads to high rates of haematological toxicity. Weekly docetaxel is associated with less haematological toxicity. This randomised phase II study tested weekly docetaxel-based combination chemotherapy regimens, with the aim of maintaining their activity while reducing toxicity.Methods:
Patients with histologically confirmed metastatic oesophageal or gastric carcinoma were randomised to receive weekly docetaxel (30 mg m−2) on days 1 and 8, cisplatin (60 mg m−2) on day 1, and 5-fluorouracil (200 mg m−2 per day) continuously, every 3 weeks (weekly TCF, wTCF); or docetaxel (30 mg m−2) on days 1 and 8 and capecitabine (1600 mg m−2 per day) on days 1–14, every 3 weeks (weekly TX, wTX).Results:
A total of 106 patients were enrolled (wTCF, n=50; wTX, n=56). Response rates, the primary end point, were 47% with wTCF and 26% with wTX. Rates of febrile neutropenia were low in each arm. Median progression-free and overall survival times were 5.9 and 11.2 months for wTCF and 4.6 and 10.1 months for wTX, respectively.Conclusion:
Weekly TCF and TX have encouraging activity and less haematological toxicity than TCF administered 3-weekly. Weekly docetaxel-based combination regimens warrant further evaluation in this disease. 相似文献4.
H Kunitoh T Tamura T Shibata K Nakagawa K Takeda Y Nishiwaki Y Osaki K Noda A Yokoyama N Saijo JCOG Lung Cancer Study Group Tokyo Japan 《British journal of cancer》2009,101(9):1549-1554
Background:
To evaluate the safety and efficacy of dose-dense weekly chemotherapy in the treatment of advanced thymoma.Methods:
Subjects comprised patients with histologically documented chemotherapy-naïve thymoma with stage-IVa or IVb disease. Thymic carcinoma, carcinoid or lymphoma cases were excluded. Patients received 9 weeks of chemotherapy: cisplatin (25 mg m−2) on weeks 1–9; vincristine (1 mg m−2) on weeks 1, 2, 4, 6 and 8; and doxorubicin (40 mg m−2) and etoposide (80 mg m−2) on days 1–3 of weeks 1, 3, 5, 7 and 9. Chemotherapy courses were supported by granulocyte colony-stimulating factor. Post-protocol local therapy was allowed.Results:
From July 1997 to March 2004, 30 patients were entered. Three were ineligible due to different histology. Chemotherapy-associated toxicity was mainly haematological and was well tolerated, with no deaths due to toxicity, and 87% of patients completed the planned 9-week regimen. Overall response rate was 59%, with 16 of the 27 eligible patients achieving partial response. Median progression-fee survival (PFS) was 0.79 years (95% confidence interval: 0.52–1.40 years), and PFS at 1 and 2 years was 37 and 15%, respectively. Overall survival rates at 2 and 5 years were 89 and 65%, respectively.Conclusion:
In stage-IV thymoma patients, weekly dose-dense chemotherapy offers similar activity to conventional regimens. 相似文献5.
Yi JH Lee J Lee J Park SH Park JO Yim DS Park YS Lim HY Kang WK 《British journal of cancer》2012,106(9):1469-1474
Background:
Docetaxel is widely used as a chemotherapeutic agent for gastric cancer treatment. A combined regimen with sunitinib demonstrated a synergistic antitumour effect in a preclinical model. The aim of this study was to evaluate the efficacy and safety of this combination in patients with unresectable or metastatic advanced gastric cancer following failure of treatment with a fluoropyrimidine and platinum combination.Methods:
This open-label, phase II, randomised trial enrolled patients with unresectable or metastatic gastric cancer. Patients were assigned to either a docetaxel monotherapy arm (D only arm: 60 mg m−2, every 3 weeks) or a combination arm (DS arm: docetaxel+sunitinib 37.5 mg every day). The primary end point of the study was time to progression and the secondary end points were overall response rate, disease control rate, overall survival, and toxicity profile. A pharmacokinetic study was also performed.Results:
A total of 107 patients were entered into the study. The TTP was not significantly prolonged in the DS arm when compared with the D only arm (DS vs D only arm: 3.9 months (95% confidence interval (CI) 2.9–4.9) vs 2.6 months (95% CI 1.8–3.5) (P=0.206). The hazard ratio for TTP was 0.77 (95% CI 0.52–1.16). However, the objective response rate was significantly higher in the DS arm (41.1% vs 14.3%, P=0.002). Patients in the DS arm experienced stomatitis, diarrhoea, and hand–foot syndrome more frequently.Conclusion:
The addition of sunitinib to docetaxel did not significantly prolong TTP, although it significantly increased response. 相似文献6.
Cristina Saura Ling‐Ming Tseng Stephen Chan Raju T. Chacko Mario Campone Alexy Manikhas Shona M. Nag Cynthia G. Leichman Lokanatha Dasappa Peter A. Fasching Fernando Hurtado de Mendoza W. Fraser Symmans David Liu Pralay Mukhopadhyay Christine Horak Guan Xing Lajos Pusztai 《The oncologist》2013,18(7):787-794
Background.
This randomized phase II trial was designed to compare the rate of pathologic complete response (pCR) induced by neoadjuvant cyclophosphamide plus doxorubicin (AC) followed by ixabepilone or paclitaxel in women with early stage breast cancer (BC). Expression of βIII-tubulin as a predictive marker was also evaluated.Patients and Methods.
Women with untreated, histologically confirmed primary invasive breast adenocarcinoma received four cycles of AC followed by 1:1 randomization to either ixabepilone 40 mg/m2 (3-hour infusion) every 3 weeks for four cycles (n = 148) or weekly paclitaxel 80 mg/m2 (1-hour infusion) for 12 weeks (n = 147). All patients underwent a core needle biopsy of the primary cancer for molecular marker analysis prior to chemotherapy. βIII-Tubulin expression was assessed using immunohistochemistry.Results.
There was no significant difference in the rate of pCR in the ixabepilone treatment arm (24.3%; 90% confidence interval [CI], 18.6–30.8) and the paclitaxel treatment arm (25.2%; 90% CI, 19.4–31.7). βIII-Tubulin-positive patients obtained higher pCR rates compared with βIII-tubulin-negative patients in both treatment arms; however, βIII-tubulin expression was not significantly associated with a differential response to ixabepilone or paclitaxel. The safety profiles of both regimens were generally similar, although neutropenia occurred more frequently in the ixabepilone arm (grade 3/4: 41.3% vs. 8.4%). The most common nonhematologic toxicity was peripheral neuropathy.Conclusions.
Neoadjuvant treatment of early stage BC with AC followed by ixabepilone every 3 weeks or weekly paclitaxel was well tolerated with no significant difference in efficacy. Higher response rates were observed among βIII-tubulin-positive patients. 相似文献7.
Miles D Roché H Martin M Perren TJ Cameron DA Glaspy J Dodwell D Parker J Mayordomo J Tres A Murray JL Ibrahim NK;Theratope® Study Group 《The oncologist》2011,16(8):1092-1100
Purpose.
This double-blind, randomized, phase III clinical trial evaluated time to progression (TTP) and overall survival in women with metastatic breast cancer (MBC) who received sialyl-TN (STn) keyhole limpet hemocyanin (KLH) vaccine. Secondary endpoints included vaccine safety and immune response.Experimental design.
The study population consisted of 1,028 women with MBC across 126 centers who had previously received chemotherapy and had had either a complete or a partial response or no disease progression. All women received one-time i.v. cyclophosphamide (300 mg/m2) 3 days before s.c. injection of 100 μg STn-KLH plus adjuvant (treatment group) or 100 μg KLH plus adjuvant (control group) at weeks 0, 2, 5, and 9. Subsequently, STn-KLH without adjuvant or KLH without adjuvant was then administered monthly for 4 months, and then quarterly until disease progression, without cyclophosphamide.Results.
STn-KLH vaccine was well tolerated; patients had mild to moderate injection-site reactions and reversible flu-like symptoms. Week-12 antibody testing revealed high specific IgG titers and a high rate of IgM-to-IgG seroconversion; the median IgG titers in STn-KLH recipients were 320 (anti-ovine submaxillary mucin) and 20,480 (anti-STn), with no detectable antimucin antibodies in the control group. The TTP was 3.4 months in the treatment group and 3.0 months in the control group. The median survival times were 23.1 months and 22.3 months, respectively.Conclusions.
Although STn-KLH was well tolerated in this largest to date metastatic breast cancer vaccine trial, no overall benefit in TTP or survival was observed. Lessons were learned for future vaccine study designs. 相似文献8.
Xiang-Yun Zong Yang Yu Hong-Jian Yang 《Journal of experimental & clinical cancer research : CR》2009,28(1):119
Background
This study was designed to explore the feasibility, safety, and outcomes of pre-operative oxaliplatin-dacarbazine combination therapy for the treatment of advanced soft tissue sarcoma (STS) of the limb.Patients and Methods
Between November 2005 and November 2008, 31 patients with advanced limb STS classified with stage IV STS were randomly assigned into experimental or control groups, and both were given 2 cycles of chemotherapy before undergoing surgery. The regimen for the experimental group was oxaliplatin (120 mg/m2, d1) in combination with dacarbazine (175 mg/m2, d1-3), while that for the control group was a standard vincristine, epirubicin, cyclophosphamide therapy. Operations were carried out four weeks after the second chemotherapy cycle, followed by another 2-4 more chemotherapy cycles of the previous regimen.Results
Following preoperative chemotherapy, the experimental group exhibited a significant improvement in tumor regression compared to controls. Both regimens were well-tolerated, and no significant differences in adverse reactions were noted. At a median follow-up of 24 months, 28 patients were still alive and had normal limb function. The progression free survival rate of the experimental group was significantly higher than that of the control group (10/15 vs. 4/16, p < 0.05).Conclusion
Oxaliplatin- dacarbazine neoadjuvant/adjuvant chemotherapy improved the prognosis of patients with advanced limb STS in comparison with vincristine, epirubicin, cyclophosphamide combination therapy. 相似文献9.
J Feliu A Salud M J Safont C García-Girón J Aparicio R Vera O Serra E Casado M Jorge P Escudero C Bosch U Bohn R Pérez-Carrión A Carmona V Martínez-Marín J Maurel 《British journal of cancer》2014,111(2):241-248
Background:
Subgroup analyses of clinical studies suggest that bevacizumab plus XELOX is effective and tolerable in elderly patients with metastatic colorectal cancer (mCRC). The prospective BECOX study examined the efficacy and safety of bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly patients with mCRC.Methods:
Patients aged ⩾70 years with Eastern Cooperative Oncology Group performance status 0 out of 1 and confirmed mCRC were included. Patients received bevacizumab 7.5 mg kg−1 and oxaliplatin 130 mg m−2 on day 1, plus capecitabine 1000 mg m−2 bid orally on days 1–14 every 21 days; oxaliplatin was discontinued after 6 cycles. The primary end point was time to progression (TTP).Results:
The intent-to-treat population comprised 68 patients (65% male, median age 76 years). Median TTP was 11.1 months; median overall survival was 20.4 months; overall response rate was 46%. Grade 3 or 4 adverse events included diarrhoea (18%) and asthenia (16%). Grade 3 or 4 adverse events of special interest for bevacizumab included deep-vein thrombosis (6%) and pulmonary embolism (4%).Conclusions:
Bevacizumab plus XELOX was effective and well tolerated in elderly patients in the BECOX study. The adverse-event profile was similar to previous reports; no new safety concerns were identified. Fit elderly patients with mCRC should be considered for treatment with bevacizumab plus XELOX. 相似文献10.
Maurício W Perroud Jr Helen N Honma Aristóteles S Barbeiro Simone CO Gilli Maria T Almeida José Vassallo Sara TO Saad Lair Zambon 《Journal of experimental & clinical cancer research : CR》2011,30(1):65
Background
Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients.Methods
Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 × 107 DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively.Results
The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together.Conclusion
Despite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment.Trial Registration
Current Controlled Trials: ISRCTN45563569 相似文献11.
DeConti RC Algazi AP Andrews S Urbas P Born O Stoeckigt D Floren L Hwang J Weber J Sondak VK Daud AI 《British journal of cancer》2010,103(10):1548-1553
Background:
Sagopilone is a novel fully synthetic epothilone with promising preclinical activity and a favourable toxicity profile in phase I testing.Methods:
A phase II pharmacokinetic and efficacy trial was conducted in patients with metastatic melanoma. Patients had measurable disease, Eastern Cooperative Oncology Group performance status 0–2, adequate haematological, and organ function, with up to 2 previous chemotherapy and any previous immunotherapy regimens. Sagopilone, 16 mg m−2, was administered intravenously over 3 h every 21 days until progression or unacceptable toxicity.Results:
Thirty-five patients were treated. Sagopilone showed multi-exponential kinetics with a mean terminal half-life of 64 h and a volume of distribution of 4361 l m−2 indicating extensive tissue/tubulin binding. Only grade 2 or lower toxicity was observed: these included sensory neuropathy (66%), leukopenia (46%), fatigue (34%), and neutropenia (31%). The objective response rate was 11.4% (one confirmed complete response, two confirmed partial responses, and one unconfirmed partial response). Stable disease for at least 12 weeks was seen in an additional eight patients (clinical benefit rate 36.4%).Conclusion:
Sagopilone was well tolerated with mild haematological toxicity and sensory neuropathy. Unlike other epothilones, it shows activity against melanoma even in pretreated patients. Further clinical testing is warranted. 相似文献12.
Jeong-Hoon Lee Yoon Lee Minjong Lee Min Kyu Heo Jae-Sung Song Ki-Hwan Kim Hyunah Lee Nam-Joon Yi Kwang-Woong Lee Kyung-Suk Suh Yong-Soo Bae Yoon Jun Kim 《British journal of cancer》2015,113(12):1666-1676
Background:
To date, no adjuvant treatment has been shown to have a clear benefit in patients with hepatocellular carcinoma (HCC). In this prospective phase I/IIa study, we evaluated the safety and efficacy of adjuvant dendritic cell (DC) therapy in HCC patients who received primary treatment for HCC.Methods:
Twelve HCC patients who had no viable tumour after primary treatments were included. Dendritic cell vaccines pulsed with cytoplasmic transduction peptide-attached alpha-fetoprotein, glypican-3 and melanoma-associated antigen 1 recombinant fusion proteins were injected subcutaneously near to inguinal lymph nodes. Adverse effects, time to progression (TTP), and associated immune responses were evaluated after DC vaccination.Results:
Nine of 12 patients had no tumour recurrence up to 24 weeks after DC vaccination. Among a total of 144 adverse events, 129 events (89.6%) were regarded as adverse drug reactions, all of which were grade 1 or 2. The majority of patients showed enhanced anti-tumour immune responses after DC vaccination. Recurrence-free patients exhibited relatively stronger anti-tumour immune responses than patients who developed recurrence after DC vaccination, as evidenced by lymphocyte proliferation and IFN-γ ELISPOT assays. The median time of TTP was 36.6 months in the DC-vaccination group and 11.8 months in the control group (hazard ratio, 0.41; 95% confidence interval, 0.18–0.95; P=0.0031 by log-rank test).Conclusions:
Adjuvant DC vaccine for HCC was safe and well tolerated in phase I/IIa study, and preliminary efficacy data are encouraging to warrant further clinical study in patients with HCC after primary treatments. 相似文献13.
M Toi H Iwata Y Fujiwara Y Ito S Nakamura Y Tokuda T Taguchi Y Rai K Aogi T Arai J Watanabe T Wakamatsu K Katsura C E Ellis R C Gagnon K E Allen Y Sasaki S Takashima 《British journal of cancer》2009,101(10):1676-1682
Background:
HER2-positive metastatic breast cancer (MBC) relapsing after trastuzumab-based therapy may require continued HER2 receptor inhibition to control the disease and preserve the patients'' quality-of-life. Efficacy and safety of lapatinib monotherapy was evaluated in Japanese breast cancer patients after trastuzumab-based therapies.Methods:
In studies, EGF100642 and EGF104911 evaluated the efficacy and safety of oral lapatinib given 1500 mg once daily in patients with advanced or MBC. All patients progressed on anthracyclines and taxanes; HER2-positive patients had also progressed on trastuzumab.Results:
For HER2-positive tumours (n=100), objective response rate was 19.0% (95% confidence interval (CI): 11.8–28.1) and clinical benefit rate (CBR) was 25.0% (95% CI: 16.9–34.7). One out of 22 HER2-negative tumour was documented as complete response (n=22). The median time-to-progression (TTP) in the HER2-positive and HER2-negative groups was 13.0 and 8.0 weeks (P=0.007); median overall survival was 58.3 and 40.0 weeks, respectively. The most frequent adverse event was diarrhoea. TTP and CBR were significantly associated with HER2 expression. Patients with tumours harbouring an H1047R PIK3CA mutation or low expression of PTEN derived clinical benefit from lapatinib.Conclusion:
Lapatinib monotherapy had shown anti-tumour activity in Japanese patients with HER2-positive MBC that relapsed after trastuzumab-based therapy, including those with brain metastases. Patients benefiting from lapatinib may have biomarker profiles differing from that reported for trastuzumab. 相似文献14.
K K Y Cham J H E Baker K S Takhar J A Flexman M Q Wong D A Owen A Yung P Kozlowski S A Reinsberg E M Chu C-W A Chang A K Buczkowski S W Chung C H Scudamore A I Minchinton D T T Yapp S S W Ng 《British journal of cancer》2010,103(1):52-60
Background:
The current standard of care for pancreatic cancer is weekly gemcitabine administered for 3 of 4 weeks with a 1-week break between treatment cycles. Maximum tolerated dose (MTD)-driven regimens as such are often associated with toxicities. Recent studies demonstrated that frequent dosing of chemotherapeutic drugs at relatively lower doses in metronomic regimens also confers anti-tumour activity but with fewer side effects.Methods:
Herein, we evaluated the anti-tumour efficacy of metronomic vs MTD gemcitabine, and investigated their effects on the tumour microenvironment in two human pancreatic cancer xenografts established from two different patients.Results:
Metronomic and MTD gemcitabine significantly reduced tumour volume in both xenografts. However, Ktrans values were higher in metronomic gemcitabine-treated tumours than in their MTD-treated counterparts, suggesting better tissue perfusion in the former. These data were further supported by tumour-mapping studies showing prominent decreases in hypoxia after metronomic gemcitabine treatment. Metronomic gemcitabine also significantly increased apoptosis in cancer-associated fibroblasts and induced greater reductions in the tumour levels of multiple pro-angiogenic factors, including EGF, IL-1α, IL-8, ICAM-1, and VCAM-1.Conclusion:
Metronomic dosing of gemcitabine is active in pancreatic cancer and is accompanied by pronounced changes in the tumour microenvironment. 相似文献15.
H Kunitoh T Tamura T Shibata K Takeda N Katakami K Nakagawa A Yokoyama Y Nishiwaki K Noda K Watanabe N Saijo 《British journal of cancer》2010,103(1):6-11
Background:
This study aimed to evaluate the safety and efficacy of dose-dense weekly chemotherapy, followed by resection and/or thoracic radiotherapy.Methods:
Patients with histologically documented thymoma with unresectable stage III disease received 9 weeks of chemotherapy: cisplatin 25 mg m−2 on weeks 1–9; vincristine 1 mg m−2 on weeks 1, 2, 4, 6 and 8; and doxorubicin 40 mg m−2 and etoposide 80 mg m−2 on days 1–3 of weeks 1, 3, 5, 7 and 9. Patients went on to surgery and post-operative radiotherapy of 48 Gy; those with unresectable disease received 60 Gy radiotherapy.Results:
total of 23 patients were entered. The main toxicities of the chemotherapy regimen were neutropenia and anaemia, and 57% of patients completed the planned 9 weeks of therapy. There were no toxic deaths. Of the 21 eligible patients, 13 (62%) achieved a partial response (95% confidence interval: 38–82%). Thirteen patients underwent a thoracotomy and nine (39%) underwent complete resection. Progression-free survival at 2 and 5 years was 80 and 43%, respectively. Overall survival at 5 and 8 years was 85 and 69%, respectively. Survival did not seem to be affected by resection.Conclusion:
In thymoma patients, weekly dose-dense chemotherapy has activity similar to that of conventional regimens. Although some patients could achieve complete resection, the role of surgery remains unclear. 相似文献16.
Background.
Recurrence of hepatocellular carcinoma (HCC) is a major problem after surgical or ablative treatments. The aim of this prospective, single-center, placebo-controlled, randomized, double-blind clinical study was to evaluate the effectiveness of transarterial chemoembolization (TACE) combined with sorafenib as a sequential treatment regimen in delaying time to progression (TTP) of intermediate-stage HCC in patients with chronic hepatitis C virus (HCV) infection.Material and Methods.
Between October, 2007 and January, 2011, 80 HCV-infected patients with Barcelona Clinic Liver Cancer stage B HCC underwent the TACE procedure. All had Child-Pugh class A disease. They were randomized 1:1 to receive sorafenib at a dose of 400 mg twice daily or placebo. Endpoints were the TTP and the rates of adverse events and toxicity.Results.
Sixty-two of 80 patients (77%), 31 in the sorafenib group and 31 in the control group, completed the study. The median TTP was 9.2 months in the sorafenib group and 4.9 months in the placebo group (hazard ratio, 2.5; 95% confidence interval, 1.66–7.56; p < .001). Metachronous, multicentric HCC progression occurred less frequently in sorafenib-treated patients (p < .05). Adverse reactions to sorafenib caused withdrawal from the study of 9 (22%) patients.Conclusion.
A conventional TACE procedure followed by sorafenib treatment resulted in a significantly longer TTP in patients with intermediate-stage HCV-related HCC, with no unexpected side effects. 相似文献17.
Hope E. Uronis Johanna C. Bendell Ivy Altomare Gerard C. Blobe S. David Hsu Michael A. Morse Herbert Pang S. Yousuf Zafar Paul Conkling Justin Favaro Christy C. Arrowood Stephanie M. Cushman Kellen L. Meadows John C. Brady Andrew B. Nixon Herbert I. Hurwitz 《The oncologist》2013,18(3):271-272
Background.
Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas.Methods.
Thirty-seven patients with metastatic or unresectable gastric/gastroesophageal junction tumors were enrolled and treated with capecitabine 850 mg/m2 BID on days 1–14, and oxaliplatin 130 mg/m2 with bevacizumab 15 mg/kg on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Neuropilin-1 (NRP1) and -2 (NRP2) mRNA expression was evaluated in archived tumor.Results.
Thirty-five patients were evaluable for efficacy. Median PFS was 7.2 months; median OS was 10.8 months. RR was estimated at 51.4%. The regimen was tolerable with expected drug class-related toxicities. NRP2 mRNA levels significantly correlated with PFS (p = 0.042) and showed a trend toward significance with OS (p = 0.051). Nonsignificant trends for NRP1 were noted for higher expression levels and worse outcome.Conclusions.
Bevacizumab can be given safely with chemotherapy in patients with metastatic esophagogastric adenocarcinomas. The combination of capecitabine, oxaliplatin, plus bevacizumab has activity comparable to other bevacizumab-containing regimens in metastatic gastroesophageal cancer. 相似文献18.
Brigitte C. Widemann Eva Dombi Andrea Gillespie Pamela L. Wolters Jean Belasco Stewart Goldman Bruce R. Korf Jeffrey Solomon Staci Martin Wanda Salzer Elizabeth Fox Nicholas Patronas Mark W. Kieran John P. Perentesis Alyssa Reddy John J. Wright AeRang Kim Seth M. Steinberg Frank M. Balis 《Neuro-oncology》2014,16(5):707-718
Background
RAS is dysregulated in neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PNs). The activity of tipifarnib, which blocks RAS signaling by inhibiting its farnesylation, was tested in children and young adults with NF1 and progressive PNs.Methods
Patients aged 3–25 years with NF1-related PNs and imaging evidence of tumor progression were randomized in a double-blinded fashion to receive tipifarnib (200 mg/m2 orally every 12 h) or placebo (phase A) and crossed over to the opposite treatment arm at the time of tumor progression (phase B). PN volumes were measured with MRI, and progression was defined as ≥20% volume increase. Time to progression (TTP) in phase A was the primary endpoint, and the trial was powered to detect whether tipifarnib doubled TTP compared with placebo. Toxicity, response, and quality of life were also monitored.Results
Sixty-two patients were enrolled. Tipifarnib and placebo were well tolerated. On phase A, the median TTP was 10.6 months on the placebo arm and 19.2 months on the tipifarnib arm (P = .12; 1-sided). Quality of life improved significantly compared with baseline on the tipifarnib arm but not on the placebo arm. Volumetric tumor measurement detected tumor progression earlier than conventional 2-dimensional (WHO) and 1-dimensional (RECIST) methods.Conclusions
Tipifarnib was well tolerated but did not significantly prolong TTP of PNs compared with placebo. The randomized, flexible crossover design and volumetric PN assessment provided a feasible and efficient means of assessing the efficacy of tipifarnib. The placebo arm serves as an historical control group for phase 2 single-arm trials directed at progressive PNs. 相似文献19.
Cai W Maldonado NV Cui W Harutyunyan N Ji L Sposto R Reynolds CP Keshelava N 《British journal of cancer》2010,103(9):1369-1379
Background:
The combination of temozolomide (TMZ) and irinotecan is a regimen used in neuroblastoma patients with recurrent disease. O6-methylguanine-DNA methyltransferase (MGMT) may have a function in resistance to TMZ. Using neuroblastoma pre-clinical models, we determined whether the inhibition of MGMT by O6-benzylguanine (O6-BG) could enhance the anti-tumour activity of TMZ and irinotecan.Methods:
The cytotoxicity of TMZ and irinotecan, either alone or in combination, was measured in five neuroblastoma cell lines in the presence or absence of O6-BG with a fluorescence-based cell viability assay (DIMSCAN). Anti-tumour activity was measured in three neuroblastoma xenograft models.Results:
MGMT mRNA and protein were expressed in 9 out of 10 examined cell lines. Pretreatment of cells with 25 μ O6-BG decreased MGMT protein expression and enhanced The TMZ cytotoxicity by up to 0.3–1.4 logs in four out of five tested cell lines. TMZ (25 mg kg−1 per day for 5 days every 3 weeks for four cycles) did not significantly improve mice survival, whereas the same schedule of irinotecan (7.5 mg kg−1 per day) significantly improved survival (P<0.0001) in all three xenograft models. Combining O6-BG and/or TMZ with irinotecan further enhanced survival.Conclusion:
Our in vitro and in vivo findings suggest that irinotecan drives the activity of irinotecan and TMZ in recurrent neuroblastoma. Inhibitors of MGMT warrant further investigation for enhancing the activity of regimens that include TMZ. 相似文献20.
Parvin F. Peddi May Cho Jian Wang Feng Gao Andrea Wang-Gillam 《Journal of gastrointestinal oncology.》2013,4(4):370-373