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The Significance of Sidedness in Patients with Metastatic Colorectal Cancer Treated with Triplet First-line Chemotherapy.

ABSTRACT: BACKGROUND:Recent data have shown that right-sided colon cancer carries poorer prognosis compared to left-sided tumors. This study was aimed to evaluate the progression-free survival, overall survival of patients with metastatic colon cancer of right-sided versus left-sided primaries treated with triplet chemotherapy regimen. METHODS:The medical records of patients with metastatic colorectal cancer treated on phase I-II trial of combination Irinotecan, oxaliplatin, capecitabine, and bevacizumab were reviewed for sidedness of the primary. The analysis was performed for progression-free survival and overall survival according to the sidedness and other known prognostic factors. RESULTS:Out of 53 patients treated with triplet therapy, 11 had right sided and 42 had left-sided primaries. The median age for right-sided primaries was 46 (range 24-55) compared to 53 (range 32-74) in left-sided primaries. Median progression-free survival was 14 months for right vs 18 months for left sided tumors (Hazard ratio 0.72, 95% confidence interval 0.27-1.88, p=0.492) and median overall survival was 21 months for right vs 29 months for left sided tumors (Hazard ratio was 0.86, 95% CI 0.32-2.26, p=0.752). CONCLUSION:First-line triplet chemotherapy may overcome the difference in prognosis between right sided and left sided primaries in metastatic colorectal cancer. A larger analysis is warranted.

SUBMITTER: Bazarbashi S

PROVIDER: S-EPMC6982651 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The Significance of Sidedness in Patients with Metastatic Colorectal Cancer Treated with Triplet First-line Chemotherapy.

Bazarbashi Shouki S Omar Ayman T AT Raddaoui Leen L Badran Ahmed A Alzahrani Ahmed A Aljubran Ali A Elhassan Tusneem T

Asian Pacific journal of cancer prevention : APJCP 20191001 10

<h4>Background</h4>Recent data have shown that right-sided colon cancer carries poorer prognosis compared to left-sided tumors. This study was aimed to evaluate the progression-free survival, overall survival of patients with metastatic colon cancer of right-sided versus left-sided primaries treated with triplet chemotherapy regimen.<h4>Methods</h4>The medical records of patients with metastatic colorectal cancer treated on phase I-II trial of combination Irinotecan, oxaliplatin, capecitabine, a ...[more]

PMID: 31653131

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Project description:BackgroundSurgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here, we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC.Patients and methodsPatients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of capecitabine, oxaliplatin, irinotecan, and bevacizumab. Patients were given 5-8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity, or patient request. All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and 2 monthly intervals thereafter. Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy.ResultsFifty-three patients were enrolled. The median age was 52 years (range 23-74), 29 (55%) were males, ECOG PS 0-1 was 13 (66%), 11 (42%) had a right-sided tumor, 29 (55%) had resection of their primary tumor, 22 (42%) had a single metastatic site, and 8 (15.1%) had a liver-limited disease. Thirteen patients (24.5%) underwent surgical resection of residual metastatic disease +/- the primary tumor with 10 (18.9%) of them were R0. The surgical group had a higher incidence of males compared to the non-surgical group (69.3% vs 47.2%, p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p = 0.09), higher mutant Kras (53.8% vs 34.2%, p = 0.3), and higher response rate (84.6% vs 56.2%, p = 0.3). With a median follow-up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI) 9.1-20] and the median OS was 28.2 months (95% CI 22.5-53.3). The median PFS for the surgery group was 18.9 months (95% CI 12.6-not reached) compared to 9.6 months (95% CI 7.0-18.3) for the non-surgical group, log-rank p = 0.0165. The median OS for both groups was not reached (95% CI 53.3-not reached) and 23.2 months (95% CI 17.0-28.4) respectively, log-rank p = 0.0006. Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively.ConclusionsPatients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible.Trial registrationClinicaltrials.gov , NCT01311050 , registered March 6, 2011, retrospectively registered.

Project description:BACKGROUND:No biomarkers exist to predict benefit from antiangiogenic therapy in metastatic colorectal cancer patients. ACVRL1 (activin receptor like-protein 1) encodes for ALK1, a member of the transforming growth factor-? receptor family, which directs pathologic angiogenesis. We examined the intratumoral expression of ACVRL1 and other angiogenesis pathway-related genes to identify molecular markers in the TRIBE study. MATERIALS AND METHODS:Of 503 randomized patients, 228 had sufficient tissue for analysis. Formalin-fixed paraffin-embedded specimens were examined for expression of VEGF-A, VEGF-B, VEGF-C, VEGFR1, VEGFR2, ACVRL1, EphB4, and EGFL7 using reverse transcription polymerase chain reaction. A maximal ?2 approach was used to determine the messenger RNA levels associated with progression-free survival (PFS), overall survival (OS), response rate, early tumor shrinkage, and depth of response. Recursive partitioning trees were constructed to identify composite prognostic biomarker profiles. External validation was conducted in silico using the Oncomine database. RESULTS:High ACVRL1 expression was associated with superior OS in both treatment arms (FOLFOXIRI [5-fluorouracil, leucovorin, oxaliplatin, irinotecan]-bevacizumab, 32.7 vs. 13.5 months, hazard ratio [HR], 0.38, P = .023; FOLFIRI [5-fluorouracil, leucovorin, irinotecan]-bevacizumab, 35.1 vs. 22.0 months, HR, 0.36, P = .006) and prolonged PFS (11.7 vs. 5.9 months, multivariate HR, 0.17; P = .001) for patients receiving FOLFOXIRI-bevacizumab on univariate and multivariate analyses. In recursive partitioning analysis, ACVRL1 was the strongest discriminator of the response rate, PFS, and OS in patients receiving FOLFOXIRI-bevacizumab and of OS in patients receiving FOLFIRI-bevacizumab. In silico validation revealed significant associations between ACVRL1 expression, disease recurrence, and 1-year survival (P < .05) among all colorectal cancer stages. CONCLUSION:ACVRL1 expression could serve as a prognostic biomarker in metastatic colorectal cancer patients receiving chemotherapy and bevacizumab and warrants further evaluation in prospective studies.

Dataset Information

The Significance of Sidedness in Patients with Metastatic Colorectal Cancer Treated with Triplet First-line Chemotherapy.

Publications

The Significance of Sidedness in Patients with Metastatic Colorectal Cancer Treated with Triplet First-line Chemotherapy.

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