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Bevacizumab plus chemotherapy as third- or later-line therapy in patients with heavily treated metastatic colorectal cancer.

Yang Q, Yin C, Liao F, Huang Y, He W, Jiang C, Guo G, Zhang B, Xia L - Onco Targets Ther (2015)

Bottom Line: The common bevacizumab-associated toxicity was hypertension (31.4%).None of the patients discontinued therapy or died because of bevacizumab-associated toxicities.In addition, preliminary data suggested that primary colon cancer was more likely to benefit from bevacizumab-containing regimens.

View Article: PubMed Central - PubMed

Affiliation: VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China ; Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, People's Republic of China ; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.

ABSTRACT

Background: Currently available third- or later-line therapy for metastatic colorectal cancer (mCRC) is limited in its efficacy, with a weak survival benefit in patients who progressed after two or more lines of standard therapy. Our retrospective study aimed to explore the value of bevacizumab plus chemotherapy in this setting.

Methods: Patients with mCRC who received fluoropyrimidine, oxaliplatin, and irinotecan as first- and second-line chemotherapy were selected for inclusion. Treatment consisted of bevacizumab plus chemotherapy. Chemotherapy consisted mainly of oxaliplatin, irinotecan, and fluoropyrimidine.

Results: Between February 2010 and December 2012, 35 consecutive patients with mCRC were treated with bevacizumab plus chemotherapy as a third- or later-line treatment. No complete responses, seven partial responses (20%), 22 stable disease responses (62.9%), and six progressive disease responses (17.1%) were obtained, producing an objective response rate of 20% and a disease control rate of 82.9%. With a median follow-up of 11.3 months (range: 0.7-48.0 months), the median progression-free survival was 5.98 months (95% confidence interval: 4.76-7.2 months), and the median overall survival was 14.77 months (95% confidence interval: 11.45-18.1 months). In the univariate analysis, patients with a primary colon tumor might have had a longer overall survival than patients with a primary rectal tumor (18.8 months vs 11.1 months, respectively; P=0.037). Common chemotherapy-related toxicities were nausea/vomiting (48.6%), fatigue (34.3%), leucopenia (40%), neutropenia, (42.9%), and anemia (42.9%), with one patient with grade 3 neutropenia, and two patients with grade 3 thrombocytopenia. The common bevacizumab-associated toxicity was hypertension (31.4%). None of the patients discontinued therapy or died because of bevacizumab-associated toxicities.

Conclusion: Our data showed that adding bevacizumab to third- or later-line therapy might lead to tumor control and improved survival in heavily pretreated mCRC patients. In addition, preliminary data suggested that primary colon cancer was more likely to benefit from bevacizumab-containing regimens. Toxicities were acceptable, and no new toxicity was identified. Further studies are needed to validate these findings.

No MeSH data available.


Related in: MedlinePlus

Kaplan–Meier estimates of progression-free (A) and overall survival (B).Notes: (A) Median progression-free survival: 5.98 months, 95% confidence interval: 4.76–7.2 months. (B) Median overall survival: 14.77 months, 95% confidence interval: 11.45–18.1 months.
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f1-ott-8-2407: Kaplan–Meier estimates of progression-free (A) and overall survival (B).Notes: (A) Median progression-free survival: 5.98 months, 95% confidence interval: 4.76–7.2 months. (B) Median overall survival: 14.77 months, 95% confidence interval: 11.45–18.1 months.

Mentions: Of the 35 patients, 100% (35/35) and 62.9% (22/35) of patients had experienced progression or died at the last follow-up. The median number of cycles of bevacizumab treatment was 6 (range: 2–17). Treatment discontinuation was caused by disease progression (29/35, 82.9%), inability to tolerate treatment (2/35, 5.7%), palliative surgery (3/35, 8.6%), or another reason (1/35, 2.9%). The response rates were as follows: no patient had a complete response, seven patients had a partial response (PR) (20%), 22 patients had stable disease (62.9%), and six patients had progressive disease (17.1%), giving an ORR of 20% and a disease control rate of 82.9% (Table 2). The median PFS was 5.98 months with a 95% confidence interval of 4.76–7.2 months. The median OS was 14.77 months with a 95% confidence interval of 11.45–18.1 months (Figure 1). In the univariate analysis, the patient’s age, sex, number of metastatic sites, status of Kirsten rat sarcoma viral oncogene (KRAS) mutation, prior anti-VEGF or anti-EGFR treatment, and pretreatment lactate dehydrogenase (LDH) level were not associated with PFS or OS. The OS was 18.56 and 13.77 months for patients treated with or without prior anti-VEGF, respectively; however, there was no statistically significant difference (P=0.58). However, the ORR (all PR) was 42.9% (6/14) in pretreatment high-LDH-level patients, which was higher than the 4.8% (1/21) ORR in pretreatment low-LDH-level patients (P=0.01). Patients with a primary colon tumor may have had a longer OS than patients with a primary rectal tumor, but the PFS was not prolonged (median OS: 18.8 months vs 11.1 months, respectively; P=0.037).


Bevacizumab plus chemotherapy as third- or later-line therapy in patients with heavily treated metastatic colorectal cancer.

Yang Q, Yin C, Liao F, Huang Y, He W, Jiang C, Guo G, Zhang B, Xia L - Onco Targets Ther (2015)

Kaplan–Meier estimates of progression-free (A) and overall survival (B).Notes: (A) Median progression-free survival: 5.98 months, 95% confidence interval: 4.76–7.2 months. (B) Median overall survival: 14.77 months, 95% confidence interval: 11.45–18.1 months.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562721&req=5

f1-ott-8-2407: Kaplan–Meier estimates of progression-free (A) and overall survival (B).Notes: (A) Median progression-free survival: 5.98 months, 95% confidence interval: 4.76–7.2 months. (B) Median overall survival: 14.77 months, 95% confidence interval: 11.45–18.1 months.
Mentions: Of the 35 patients, 100% (35/35) and 62.9% (22/35) of patients had experienced progression or died at the last follow-up. The median number of cycles of bevacizumab treatment was 6 (range: 2–17). Treatment discontinuation was caused by disease progression (29/35, 82.9%), inability to tolerate treatment (2/35, 5.7%), palliative surgery (3/35, 8.6%), or another reason (1/35, 2.9%). The response rates were as follows: no patient had a complete response, seven patients had a partial response (PR) (20%), 22 patients had stable disease (62.9%), and six patients had progressive disease (17.1%), giving an ORR of 20% and a disease control rate of 82.9% (Table 2). The median PFS was 5.98 months with a 95% confidence interval of 4.76–7.2 months. The median OS was 14.77 months with a 95% confidence interval of 11.45–18.1 months (Figure 1). In the univariate analysis, the patient’s age, sex, number of metastatic sites, status of Kirsten rat sarcoma viral oncogene (KRAS) mutation, prior anti-VEGF or anti-EGFR treatment, and pretreatment lactate dehydrogenase (LDH) level were not associated with PFS or OS. The OS was 18.56 and 13.77 months for patients treated with or without prior anti-VEGF, respectively; however, there was no statistically significant difference (P=0.58). However, the ORR (all PR) was 42.9% (6/14) in pretreatment high-LDH-level patients, which was higher than the 4.8% (1/21) ORR in pretreatment low-LDH-level patients (P=0.01). Patients with a primary colon tumor may have had a longer OS than patients with a primary rectal tumor, but the PFS was not prolonged (median OS: 18.8 months vs 11.1 months, respectively; P=0.037).

Bottom Line: The common bevacizumab-associated toxicity was hypertension (31.4%).None of the patients discontinued therapy or died because of bevacizumab-associated toxicities.In addition, preliminary data suggested that primary colon cancer was more likely to benefit from bevacizumab-containing regimens.

View Article: PubMed Central - PubMed

Affiliation: VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China ; Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, People's Republic of China ; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.

ABSTRACT

Background: Currently available third- or later-line therapy for metastatic colorectal cancer (mCRC) is limited in its efficacy, with a weak survival benefit in patients who progressed after two or more lines of standard therapy. Our retrospective study aimed to explore the value of bevacizumab plus chemotherapy in this setting.

Methods: Patients with mCRC who received fluoropyrimidine, oxaliplatin, and irinotecan as first- and second-line chemotherapy were selected for inclusion. Treatment consisted of bevacizumab plus chemotherapy. Chemotherapy consisted mainly of oxaliplatin, irinotecan, and fluoropyrimidine.

Results: Between February 2010 and December 2012, 35 consecutive patients with mCRC were treated with bevacizumab plus chemotherapy as a third- or later-line treatment. No complete responses, seven partial responses (20%), 22 stable disease responses (62.9%), and six progressive disease responses (17.1%) were obtained, producing an objective response rate of 20% and a disease control rate of 82.9%. With a median follow-up of 11.3 months (range: 0.7-48.0 months), the median progression-free survival was 5.98 months (95% confidence interval: 4.76-7.2 months), and the median overall survival was 14.77 months (95% confidence interval: 11.45-18.1 months). In the univariate analysis, patients with a primary colon tumor might have had a longer overall survival than patients with a primary rectal tumor (18.8 months vs 11.1 months, respectively; P=0.037). Common chemotherapy-related toxicities were nausea/vomiting (48.6%), fatigue (34.3%), leucopenia (40%), neutropenia, (42.9%), and anemia (42.9%), with one patient with grade 3 neutropenia, and two patients with grade 3 thrombocytopenia. The common bevacizumab-associated toxicity was hypertension (31.4%). None of the patients discontinued therapy or died because of bevacizumab-associated toxicities.

Conclusion: Our data showed that adding bevacizumab to third- or later-line therapy might lead to tumor control and improved survival in heavily pretreated mCRC patients. In addition, preliminary data suggested that primary colon cancer was more likely to benefit from bevacizumab-containing regimens. Toxicities were acceptable, and no new toxicity was identified. Further studies are needed to validate these findings.

No MeSH data available.


Related in: MedlinePlus