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1.
Mitsugu Kochi Yuji Akiyama Tatsuya Aoki Ken Hagiwara Takao Takahashi Katsuji Hironaka Futoshi Teranishi Fumihiko Osuka Masahiro Takeuchi Masashi Fujii Toshifusa Nakajima 《Cancer chemotherapy and pharmacology》2013,72(5):1097-1102
Purpose
The purpose of this multicenter phase II study was to evaluate the efficacy and safety of a combination of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) plus bevacizumab as first-line chemotherapy in Japanese patients with metastatic colorectal cancer.Methods
Patients with metastatic colorectal cancer were eligible for enrollment. On day 1 of a 14-day cycle, patients received bevacizumab 5 mg/kg, irinotecan 150 mg/m2, and l-leucovorin 200 mg/m2 as an intravenous infusion, followed by 5-FU 400 mg/m2 as an intravenous bolus and then 5-FU 2,400 mg/m2 as an 46-h intravenous infusion. This treatment cycle was repeated. The primary endpoint was progression-free survival (PFS).Results
We enrolled 40 patients, but one withdrew consent before starting treatment. The remaining 39 patients received a total of 509 cycles of FOLFIRI plus bevacizumab (median 11 per patient; range 1–30). The median PFS was 11.5 months, the median overall survival (OS) was 22.0 months, and the 1-year OS rate was 81.8 %. All 39 patients had adverse events. Grade 3 or 4 neutropenia and stomatitis occurred in 21 (53.9 %) and 4 (10.3 %) patients, respectively.Conclusion
Our results suggest that FOLFIRI plus bevacizumab is a clinically effective regimen with a manageable toxicity profile as first-line chemotherapy in patients with metastatic colorectal cancer. 相似文献2.
Sachi Morita Keisuke Uehara Goro Nakayama Takashi Shibata Tomoyo Oguri Megumi Inada-Inoue Tomoya Shimokata Mihoko Sugishita Ayako Mitsuma Yuichi Ando 《Cancer chemotherapy and pharmacology》2013,71(2):405-411
Purpose
Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known toxic effect of hypertension. We studied possible associations between bevacizumab-related hypertension and gene polymorphisms to assure safer cancer therapy.Methods
We retrospectively studied 60 Japanese patients with metastatic colorectal cancer who had received bevacizumab-based chemotherapy. Genotypes were determined for five well-known functional single-nucleotide polymorphism of the VEGF gene at positions C-2578A, T-1498C, G-1154A, G-634C, and C936T. Hypertension was graded according to CTCAE v4.0 on the basis of home blood pressure.Results
The VEGF-2578 C/C and -1498 T/T genotypes were associated with significantly less hypertension during the first 2 months of bevacizumab-based chemotherapy (p = 0.004, p = 0.025, respectively). During the treatment period as a whole, the VEGF-2578 C/C and 936 C/C genotypes were associated with less hypertension (p = 0.031, p = 0.043, respectively). Preexisting hypertension was not associated with bevacizumab-related hypertension.Conclusions
This study demonstrated a significant relation between a lower incidence of grade 2 or higher bevacizumab-related hypertension and the VEGF-2578 C/C genotype for the entire treatment period in Japanese patients with metastatic colorectal cancer. This genotype might be useful for ensuring safer treatment of patients who receive bevacizumab-based chemotherapy. 相似文献3.
Seiya Saito Naoko Hayashi Nobutaka Sato Masaaki Iwatsuki Yoshifumi Baba Yasuo Sakamoto Yuji Miyamoto Masayuki Watanabe Minoru Yoshida Kenji Sakai Takashi Katsumori Shigeru Katahuchi Nobuyuki Shigaki Kazutaka Yamada Masami Kimura Tomio Tanigawa Sadamu Takano Masafumi Kuramoto Hideo Baba 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(4):689-695
Background
There has so far been little information on the clinical effect of bevacizumab against colorectal cancer in Japan. Hence, this study was conducted to retrospectively evaluate the safety and efficacy of bevacizumab in clinical practice.Methods
A total of 181 patients with metastatic colorectal cancer (mCRC) received bevacizumab in combination with chemotherapy at 18 hospitals in Kumamoto prefecture, Japan. We surveyed the medical records of all patients regarding the patient characteristics, objective tumor responses, and adverse events. We analyzed their overall survival and the survival benefit when continuing the administration of bevacizumab beyond disease progression (progressive disease; PD) in patients who received bevacizumab-containing 1st line therapy.Results
The response rate (RR) in all lines of therapy was 42 %. The 1st line patients showed significantly better survival in comparison to the patients who received further lines of treatment (P = 0.005). There were no significant differences in survival between the group with post-PD treatment with bevacizumab and the group with post-PD treatment without bevacizumab (P = 0.13). The most common grade 3 or greater adverse event associated with bevacizumab was hypertension (12.2 %). Especially, a high incidence of gastrointestinal (GI) perforation was shown in this study (4.4 %) and most of the patients with GI perforation had some risk factors for this complication.Conclusion
Although the survival benefit of bevacizumab in Japanese patients with mCRC was similar to that observed in previous clinical trials, this study showed a high incidence of GI perforation in comparison to previous studies. Therefore, the careful selection of patients with few risk factors for this complication is likely to lead to a greater benefit from bevacizumab treatment. 相似文献4.
Díaz-Rubio E Gómez-España A Massutí B Sastre J Abad A Valladares M Rivera F Safont MJ Martínez de Prado P Gallén M González E Marcuello E Benavides M Fernández-Martos C Losa F Escudero P Arrivi A Cervantes A Dueñas R López-Ladrón A Lacasta A Llanos M Tabernero JM Antón A Aranda E;Spanish Cooperative Group for the Treatment of Digestive Tumors 《The oncologist》2012,17(1):15-25
Purpose.
The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC).Patients and Methods.
Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety.Results.
The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0–53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand–foot syndrome, and neuropathy.Conclusion.
Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients. 相似文献5.
Katsushi Takebayashi Eiji Mekata Hiromichi Sonoda Tomoharu Shimizu Yoshihiro Endo Tohru Tani 《Cancer chemotherapy and pharmacology》2013,72(1):217-222
Purpose
We retrospectively evaluated the clinical efficacy and feasibility of a collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to guide therapy for patients with stage IV colorectal cancer (CRC).Methods
We investigated 38 patients with stage IV CRC. All patients were younger than 85 years and had untreated evaluable metastatic lesions. The primary tumors were surgically resected, and the tissue samples were investigated by CD-DST. Patients treated with in vitro sensitive drugs were defined as Group A (n = 14), while those treated with in vitro non-sensitive drugs were defined as Group B (n = 24). We evaluated response rate (RR), progression-free survival (PFS), and overall survival (OS).Results
RR was 85.71 % in Group A and 41.67 % in Group B (p = 0.0079). The median PFS was 696.5 days in Group A and 297.5 days in Group B (p = 0.0326). The median OS was 1,023.4 days in Group A and 518.5 days in Group B (p = 0.0061).Conclusions
The CD-DST can define chemoresistant and chemosensitive tumors. The use of CD-DST might be one of the tools to supplement informed consent prior to initiation of therapy. 相似文献6.
Fotios Loupakis Emilio Bria Vanja Vaccaro Federica Cuppone Michele Milella Paolo Carlini Chiara Cremolini Lisa Salvatore Alfredo Falcone Paola Muti Isabella Sperduti Diana Giannarelli Francesco Cognetti 《Journal of experimental & clinical cancer research : CR》2010,29(1):58
Background
Although the addition of bevacizumab to 1st line chemotherapy provides a significant survival benefit for advanced colorectal cancer, the magnitudes of both advantages and toxicities have not been extensively investigated.Methods
A literature-based meta-analysis was conducted; Hazard Ratios were extracted from randomized trials for primary end-points (Progression Free Survival, PFS, Overall Survival OS). The log of event-based risk ratio were derived for secondary endpoints (objective/partial response rate, ORR/PR; severe hypertension, bleeding and proteinuria). Absolute differences and the number needed to treat/harm (NNT/NNH) were calculated. A meta-regression analysis with clinical predictors and a sensitivity analysis according to the trial phase-design were conducted as well.Results
Five trials (2,728 pts) were selected. The addition of bevacizumab to 1st line chemotherapy significantly increased both PFS (although with significant heterogeneity) and OS over exclusive chemotherapy by 17.1% and 8.6% (NNT 6 and 12), regardless of the study setting (non significant interaction between phase II and III). The chance to improve PR was significantly increased by 6.5% (NNT 15), with a trend for ORR. The risk of hypertension was significantly increased by 6.2% (NNH 16). According to the meta-regression analysis, female gender and rectal primary site were significant predictors for PFS benefit.Conclusions
Notwithstanding all the concerns related to costs and the significant HTN risk, the significant outcome improvement provided by bevacizumab in first-line treatment for unselected advanced colorectal cancer patients, should be considered when choosing the appropriate up-front therapy. 相似文献7.
Alberto Farolfi Micaela Petrone Emanuela Scarpi Valentina Gallà Filippo Greco Claudia Casanova Lucia Longo Gennaro Cormio Michele Orditura Alessandra Bologna Laura Zavallone Jole Ventriglia Elisena Franzese Vera Loizzi Donatella Giardina Eva Pigozzi Raffaella Cioffi Sandro Pignata Giorgio Giorda Ugo De Giorgi 《Targeted oncology》2018,13(4):469-479
Background
The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking.Objective
The MITO group conducted a multicenter, retrospective study (MITO 24) to investigate the role of inflammatory indexes as prognostic factors and predictors of treatment efficacy in FIGO stage III–IV EOC patients treated with first-line chemotherapy alone or in combination with bevacizumab.Patients and Methods
Of the 375 patients recruited, 301 received chemotherapy alone and 74 received chemotherapy with bevacizumab. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were evaluated to identify a potential correlation with PFS and OS in both the overall population and the two treatment arms.Results
In the overall population, the PFS and OS were significantly longer in patients with low inflammatory indexes (p?<?0.0001). In multivariate analyses, the NLR was significantly associated with OS (p?=?0.016), and the PLR was significantly associated with PFS (p?=?0.024). Inflammatory indexes were significantly correlated with patient prognosis in the chemotherapy-alone group (p?<?0.0001). Patients in the chemotherapy with bevacizumab group with a high NLR had a higher PFS and OS (p?=?0.026 and p?=?0.029, respectively) than those in the chemotherapy-alone group. Conversely, PFS and OS were significantly poorer in patients with a high SII (p?=?0.024 and p?=?0.017, respectively).Conclusion
Our results suggest that bevacizumab improves clinical outcome in patients with a high NLR but may be detrimental in those with a high SII.8.
Sastre J Maestro ML Gómez-España A Rivera F Valladares M Massuti B Benavides M Gallén M Marcuello E Abad A Arrivi A Fernández-Martos C González E Tabernero JM Vidaurreta M Aranda E Díaz-Rubio E 《The oncologist》2012,17(7):947-955
Background.
The Maintenance in Colorectal Cancer trial was a phase III study to assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus chemotherapy in patients with metastatic colorectal cancer. An ancillary study was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic and/or predictive marker for efficacy endpoints.Patients and Methods.
One hundred eighty patients were included. Blood samples were obtained at baseline and after three cycles. CTC enumeration was carried out using the CellSearch® System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment.Results.
The median progression-free survival (PFS) interval for patients with a CTC count ≥3 at baseline was 7.8 months, versus the 12.0 months achieved by patients with a CTC count <3 (p = .0002). The median overall survival (OS) time was 17.7 months for patients with a CTC count ≥3, compared with 25.1 months for patients with a lower count (p = .0059). After three cycles, the median PFS interval for patients with a low CTC count was 10.8 months, significantly longer than the 7.5 months for patients with a high CTC count (p = .005). The median OS time for patients with a CTC count <3 was significantly longer than for patients with a CTC count ≥3, 25.1 months versus 16.2 months, respectively (p = .0095).Conclusions.
The CTC count is a strong prognostic factor for PFS and OS outcomes in metastatic colorectal cancer patients. 相似文献9.
Efrat Dotan Neal J. Meropol Barbara Burtness Crystal S. Denlinger James Lee David Mintzer Fang Zhu Karen Ruth Holly Tuttle Judi Sylvester Steven J. Cohen 《Journal of gastrointestinal cancer》2012,43(4):562-569
Objectives
Dual inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) demonstrated initial promise in clinical trials. This phase II study tested the efficacy and safety of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as first-line treatment for metastatic colorectal cancer patients.Methods
Patients were randomized to receive capecitabine 850 mg/m2 PO twice daily for 14 days, oxaliplatin 130 mg/m2 IV day 1, and cetuximab 400 mg/m2 IV loading dose followed by 250 mg/m2 IV days 1, 8, and 15 with (Arm A) or without (Arm B) bevacizumab 7.5 mg/kg IV day 1 every 21 days. Tumor samples were collected and retrospectively analyzed for KRAS mutation status. The primary endpoint was response rate, with time to progression (TTP) and overall survival (OS) as secondary objectives.Results
Twenty-three patients (12 in Arm A, 11 in Arm B) were enrolled onto the study. Median follow-up was 25.9 months. Both treatments were well tolerated, with expected higher rates of grade 1/2 hypertension and bleeding in Arm A. The overall response rate was 54% (36.4% in Arm A and 72.7% in Arm B). Median time to progression was 8.7 months in Arm A and 14.4 months in Arm B. The median survival was 18.0 months in Arm A and 42.5 months in Arm B. The study was prematurely terminated after other studies reported inferior outcomes with dual antibody therapy.Conclusions
Although terminated early, the study supports the detrimental effect of combining VEGF and EGFR inhibition in metastatic colorectal cancer. 相似文献10.
Herbert I. Hurwitz Niall C. Tebbutt Fairooz Kabbinavar Bruce J. Giantonio Zhong‐Zhen Guan Lada Mitchell Daniel Waterkamp Josep Tabernero 《The oncologist》2013,18(9):1004-1012
Purpose.
This analysis pooled individual patient data from randomized controlled trials (RCTs) to more thoroughly examine clinical outcomes when adding bevacizumab to chemotherapy for patients with metastatic colorectal cancer (mCRC).Patients and Methods.
Patient data were pooled from the first-line AVF2107, NO16966, ARTIST, AVF0780, AVF2192, and AGITG MAX RCTs and the second-line E3200 RCT. All analyses were based on the intent-to-treat population. To assess differences in time-to-event variables by treatment (chemotherapy with or without placebo vs. chemotherapy plus bevacizumab), stratified random-effects (overall) and fixed-effects (subgroup comparisons) models were used to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs).Results.
The analysis population comprised 3,763 patients (1,773 chemotherapy with or without placebo; 1,990 chemotherapy plus bevacizumab). The addition of bevacizumab to chemotherapy was associated with statistically significant increases in overall survival (OS; HR, 0.80; 95% CI, 0.71–0.90) and progression-free survival (PFS; HR, 0.57; 95% CI, 0.46–0.71). The effects on OS and PFS across subgroups defined by chemotherapy backbone (oxaliplatin-based, irinotecan-based), extent of disease (liver metastases only, extensive disease), age (<65, ≥65 years), Eastern Cooperative Oncology Group performance status (0, ≥1), and KRAS status (wild-type, mutant) were consistent with the overall analysis. Incidence rates of grade ≥3 hypertension, proteinuria, bleeding, wound-healing complications, gastrointestinal perforations, and thromboembolic events were increased with bevacizumab treatment.Conclusion.
The use of bevacizumab with chemotherapy resulted in statistically significant increases in OS and PFS for patients with mCRC. The PFS benefit extended across the clinically relevant subgroups examined. The observed safety profile of bevacizumab was consistent with that reported in individual trials. 相似文献11.
Background
The standard of chemotherapy regimens for advanced or metastatic gastric cancer and the clinical outcome were heterogeneous in Asian versus non-Asian countries. This study aimed to explore predictors of safety and efficacy of chemotherapy for patients with advanced or metastatic gastric cancer.Methods
Treatment group-based meta-analysis and meta-regression were performed to analyze results of randomized trials published since 2005 for advanced or metastatic gastric cancer patients who received systemic chemotherapy as first-line treatment. Data were extracted and synthesized according to the Cochrane guidelines.Results
Twenty-five trials (8 Asian, 17 Western or international) with 56 treatment groups were analyzed. Asian trials reported a lower percentage of gastroesophageal junctional carcinoma, higher percentage of diffuse-type histology, and more frequent use of second-line chemotherapy. Meta-analysis revealed significant heterogeneity both in treatment safety (grade 3–4 neutropenia and diarrhea) and efficacy [6-month progression-free survival (PFS) and 1-year overall survival (OS)]. Meta-regression analyses indicate that Asian trials are associated with an 8.2% lower incidence of grade 3–4 neutropenia and 2.1% lower incidence of grade 3–4 diarrhea. A lower percentage of patients with gastroesophageal junction carcinoma and the use of combination regimens predicted better PFS. The use of second-line chemotherapy predicts better 1-year OS, which will increase by 10% for every 10% increase in patients who received second-line chemotherapy.Conclusion
Geographic region (Asian vs. non-Asian) is an independent predictor of safety in systemic therapy for gastric cancer. 相似文献12.
Scartozzi M Giampieri R Maccaroni E Del Prete M Faloppi L Bianconi M Galizia E Loretelli C Belvederesi L Bittoni A Cascinu S 《British journal of cancer》2012,106(5):799-804
Background:
Lactate dehydrogenase (LDH) represents a predictive factor in colorectal cancer patients treated with the angiogenesis inhibitor PTK/ZK. We explored the role of pre-treatment LDH serum levels in colorectal cancer patients receiving first-line bevacizumab.Methods:
Metastatic colorectal cancer treated with first-line bevacizumab was eligible. A control group including all consecutive patients treated with chemotherapy alone was also considered. Pre-treatment LDH serum levels were collected for all cases.Results:
Median progression-free survival (PFS) in the control group for patients with high and low LDH levels was 4.2 and 8 months, respectively (P=0.0003). Median overall survival (OS) was 19.6 and 34.9 months for patients with high and low LDH levels, respectively (P=0.0014). In the bevacizumab group, partial responses were seen in 14 (58%) high-LDH and 8 (14%) low-LDH patients (P=0.0243), respectively, median PFS was 7.3 and 8.5 months, respectively (P=0.2), and median OS was 22 and 26.6 months, respectively (P=0.7).Conclusion:
High LDH levels correlated with worse prognosis. Bevacizumab seemed capable of improving clinical outcome in this specific group of patients who usually present with an adverse natural history. The improved response rate also suggests a role for LDH as a predictive marker. 相似文献13.
Background:
Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer, but to date, despite extensive research, no predictive or prognostic biomarkers for bevacizumab have been identified. The development of bevacizumab-induced arterial hypertension has recently been suggested as a potential predictive biomarker.Methods:
Blood pressure was recorded during the BOXER study, a phase II study of capecitabine, oxaliplatin (CAPOX) plus bevacizumab as peri-operative treatment in 45 patients with poor-risk colorectal liver-only metastases unsuitable for upfront resection. In this analysis, the development of bevacizumab-induced hypertension was correlated with clinical outcomes.Results:
Fifteen percent of patients developed ⩾grade 1 hypertension while receiving neoadjuvant chemotherapy, and 4% developed grade 3 hypertension. There was no correlation between the development of hypertension and radiological response rate (P=0.642), progression-free survival (P=0.644) or overall survival (P=0.480) in those who developed hypertension compared with those who did not.Conclusion:
Bevacizumab-induced hypertension did not predict radiological response or survival in our study. The results highlight a number of important issues regarding the use of hypertension as a biomarker. 相似文献14.
Österlund P Soveri LM Isoniemi H Poussa T Alanko T Bono P 《British journal of cancer》2011,104(4):599-604
Background:
Hypertension (HTN) is a common toxicity of anti-VEGF (vascular endothelial growth factor) antibody treatment. It may be a marker of VEGF signalling pathway inhibition and therefore represent a cancer biomarker in metastatic colorectal cancer (mCRC) patients treated with chemotherapy and bevacizumab.Methods:
A total of 101 consecutive patients with mCRC were treated with standard chemotherapy combined with bevacizumab at dose of 2.5 mg kg−1 per week in a single centre. The median follow-up time of the patients alive was 64 months. Blood pressure was measured before each bevacizumab infusion, and HTN was graded according to common toxicity criteria for adverse events version 3.0.Results:
Overall, 57 patients (56%) developed ⩾grade 1 HTN (median blood pressure 168/97 mm Hg), whereas 44 (44%) remained normotensive when treated with bevacizumab-containing chemotherapy regimen. Overall response rate was higher among patients with HTN (30 vs 20% P=0.025). Hypertension was associated with improved progression-free survival (10.5 vs 5.3 months; P=0.008) and overall survival (25.8 vs 11.7 months; P<0.001), and development of HTN within 3 months had an independent, prognostic influence in a multivariate landmark survival analysis together with other known mCRC prognostic factors (P=0.007). There was no association between HTN and development of thromboembolic complications.Conclusion:
Hypertension may predict outcome of bevacizumab-containing chemotherapy in mCRC. These data require confirmation in prospective studies including pharmacodynamic and pharmacokinetic analyses. 相似文献15.
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16.
Yosuke Horita Yasuhide Yamada Ken Kato Yoshinori Hirashima Kouhei Akiyoshi Kengo Nagashima Takako Nakajima Tetsuya Hamaguchi Yasuhiro Shimada 《International journal of clinical oncology / Japan Society of Clinical Oncology》2012,17(6):604-609
Objective
FOLFIRI is a standard chemotherapy regimen for the treatment of metastatic colorectal cancer. Although some studies have shown its efficacy in combination with bevacizumab as first-line chemotherapy, there are no data to support FOLFIRI plus bevacizumab as second-line chemotherapy in patients with this form of cancer. The aim of this study was to evaluate the efficacy and safety of FOLFIRI and bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer.Methods
Eligible patients were ??20?years old, previously treated (except with irinotecan [CPT-11] and bevacizumab), with an Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and adequate organ function. Twenty-five eligible patients received FOLFIRI with bevacizumab at a dose of 10?mg/kg given intravenously on day 1. All therapy was administered every 2?weeks until disease progression. The primary endpoint was the response rate.Results
Twenty-five patients were enrolled between February 2008 and March 2009. The median age was 62 (range 38?C73) years, the male/female distribution was 20/5, 16 patients had performance status 0 and 9 had performance status 1, and the proportion of patients who were oxaliplatin pretreated/untreated was 16/9. The overall response rate was 32% (90% confidence interval [CI]: 17.0?C50.4%), with 8 patients showing partial responses, 15 with stable disease, and 2 with disease progression. Median progression-free survival was 11.6?months (95% CI: 6.9?C16.4). Median overall survival was 21.4?months (95% CI: 12.0?C30.8). The grade 3/4 adverse events with treatment were neutropenia (64%), leukopenia (16%), diarrhea (8%), anorexia (8%), and febrile neutropenia (8%). The bevacizumab-related grade 3/4 adverse event was hypertension, which was observed in 12% of patients.Conclusions
The FOLFIRI plus bevacizumab regimen is an active, well-tolerated second-line chemotherapy treatment for patients with metastatic colorectal cancer. 相似文献17.
J. Garde-Noguera M. Gil-Raga E. Evgenyeva J. A. García A. Llombart-Cussac C. Camps-Herrero 《Clinical & translational oncology》2016,18(4):405-412
Purpose
To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab.Methods
Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0–1) vs. group 2 with high expression (2–3).Results
Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy.Conclusions
Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab.18.
A J Weickhardt D S Williams C K Lee F Chionh J Simes C Murone K Wilson M M Parry K Asadi A M Scott C J A Punt I D Nagtegaal T J Price J M Mariadason N C Tebbutt 《British journal of cancer》2015,113(1):37-45
Background:
Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and receptors to determine their prognostic and predictive effects.Methods:
We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population.Results:
Patients with low expression of VEGF-D (0, 1+) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CB+CBM), 0.21; 95% CI, 0.08–0.55; overall survival (OS) HR, 0.35; 95% CI, 0.13–0.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2+ PFS HR, 0.67; 95% CI, 0.45–1.00; OS HR, 0.82; 95% CI, 0.52–1.30; VEGF-D 3+ PFS HR, 0.77; 95% CI, 0.50–1.17; OS HR, 1.28; 95% CI, 0.79–2.09) (P interaction <0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression.Conclusions:
The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation. 相似文献19.
Fogelman D Jafari M Varadhachary GR Xiong H Bullock S Ozer H Lin E Morris J Cunningham P Bennett B Abbruzzese JL Wolff RA 《Cancer chemotherapy and pharmacology》2011,68(6):1431-1438
Purpose
The gemcitabine and oxaliplatin (GEMOX) has yielded among the longest progression-free survival durations in patients with advanced pancreatic cancer (APC). We postulated that adding bevacizumab would increase the effectiveness of GEMOX.Methods
Eligible patients had stage III or IV pancreatic cancer, ECOG PS 0-2, and no prior gemcitabine. Treatment included 1,000?mg/m2 intravenous gemcitabine over 100?min on day 1, 10?mg/kg intravenous bevacizumab on day 1, and 100?mg/m2 oxaliplatin given on day 2. Cycles were repeated every 2?weeks. CT imaging was performed every 6?weeks.Results
Fifty patients were enrolled: 14 had stage III disease, the remainder stage IV. Median age was 59?years. Fourty-five patients were ECOG 0-1. The grade 3?C4 toxicity rate was 94%; fatigue (47%) and nausea (40%) were frequent. One patient died after a bowel perforation; a second died of a CVA. The median PFS was 4.9?months; median survival was 11.9?months; 1?year survival was 42%. Locally advanced patients lived 12.8?months; metastatic patients lived 10.2?months. Patients developing grade 3 hypertension were more likely to have a radiologic response (P?=?.012); survival among the top and bottom quintiles of hypertension was 14.7 and 6.2?months, respectively. Survival correlated with baseline CA 19?C9 (P?=?.004) and radiologic response. The overall response rate was 36%; 34% demonstrated stable disease.Conclusions
The GEMOX/bevacizumab regimen demonstrated an excellent median overall survival but did not meet our objective of a 14?month median survival. Toxicity was significant. We do not recommend further evaluation of this regimen. 相似文献20.
Herbert I. Hurwitz Pamela S. Douglas John P. Middleton George W. Sledge David H. Johnson David A. Reardon Dafeng Chen Oliver Rosen 《The oncologist》2013,18(3):273-280