Chemotherapy for Metastatic Colorectal Cancer

The past decade has seen a significant survival improvement for patients with metastatic colorectal cancer, fueled in large part by the arrival of active novel chemotherapeutic drugs and their incorporation into combination regimens. Several randomized trials have successfully integrated oxaliplatin and irinotecan into previously existing 5-fluorouracil (5-FU)-based regimens for advanced colorectal cancer, resulting in median survivals that have risen from 9 months to almost 2 years. Even as the ideal combinations and sequences of these regimens are elucidated, targeted therapies such as recently approved bevacizumab and cetuximab have been added to treatment protocols, with favorable consequences. We review the evolution of primary chemotherapy for advanced colorectal cancer, focusing on the trials that have led to the new standard first-line treatments. We also review the data on newer targeted therapies, especially in combination with cytotoxic therapy.

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Maintenance treatment with cetuximab in a series of patients treated with standard chemotherapy and cetuximab in metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.624 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 624-624

Author(s):

G. Quintero-Aldana ◽

S. Varela ◽

B. Campos ◽

S. Vazquez-Estevez ◽

O. Maseda ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Disease Progression ◽

Advanced Colorectal Cancer ◽

Single Agent ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Standard Chemotherapy ◽

Cutaneous Toxicity

624 Background: New strategies are needed to improve outcomes and reduced toxicities of currently treatments for patients with advanced colorectal cancer. Nowadays maintaining treatment until disease progression is the standard option for these patients. Cetuximab is a recombinant humanized monoclonal antibody that neutralizes epidermal growth factor receptor and it has shown benefit not only in combination with standard chemotherapy in first- and second-line treatment or as a single agent in progression to standard chemotherapy in KRAS wild-type metastatic colorectal cancer (mCRC). Methods: This data describes patients who received standard chemotherapy with cetuximab every two weeks. For patients with response or stable disease, cetuximab was continued until disease progression or unacceptable toxicity. Results: Twelve patients are reported, nine were male (75%). The median age was 62 years (range, 46 to 78 years). All patients had stage IV, and liver was the most common location (75%). The majority of patients (75%) received FOLFOX VI as a first-line treatment in combination with cetuximab; only two patients were treated with FOLFIRI. Cetuximab was maintained after the first line of treatment in the 75% of patients. The median of cycles of chemotherapy and cetuximab was 12. Best response achieved in this setting was complete response (58.3%, 7/12). Median of monotherapy with cetuximab treatment was 7.5 cycles (range 3 to 12). At the moment of this analysis seven of twelve patients continued with the maintenance. In the rest of patients the treatment was followed until progression (33%, 3/12). No grade 3-4 toxicities were seen during maintenance cetuximab. The most common adverse effect during maintenance was cutaneous toxicity but the majority of patients had minor toxicity (50% grade 1). Conclusions: Cetuximab has significant antitumor activity not only as a single agent or in combination with standard chemotherapy but may also when it is used as maintenance therapy after a complete or partial response to first or second line based chemotherapy in mCRC. Maintenance cetuximab is feasible, safe, and worthy of future study in advanced colorectal cancer. No significant financial relationships to disclose.

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Use of VEGF expression to predict for first-line treatment chemotherapy regimen in metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14695 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14695-e14695

Author(s):

Metin Ozkan ◽

Veli Berk ◽

Kemal Deniz ◽

Halit Karaca ◽

Mevlude Inanc ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Survival Rates ◽

First Line ◽

Vegf Expression ◽

Treatment Protocols ◽

Primary Tumors ◽

Study Results ◽

Low Expression

e14695 Background: In metastatic colorectal cancer treatment more successful results are achieved by adding anti-angiogenic therapy to the chemotherapy. Over expression of VEGF in colorectal cancer is known to be a poor prognosis factor but its effects on designating the therapy is not clear. In this study, results of the patients receiving FOLFIRI + Bevacizumab or XELOX + Bevacizumab were compared for VEGF expression. Methods: VEGF was assessed immunohistochemically in primary tumors of the 53 metastatic colorectal cancers. Severity and conformity of VEGF expression was evaluated. Results were used to assess the association with the therapy response, progression free survival (PFS) and overall survival (OS). Results: The median age of the patients was 55 (range, 32-79). In combination with bevacizumab 38 patients received FOLFIRI and 15 patients received XELOX. In 30 patients (57%) there was a strong expression of VEGF and in 23 patients (23%) the expression was weak. In the high VEGF expression group, PFS was 11 months in FOLFIRI receiving patients and 8 months in XELOX receiving ones but in low expression group PFS was 8 months in patients receiving either one of the two treatment protocols. In high expression group, PFS in FOLFIRI-bevacizumab combination receiving patients was different and this difference was statistically significant (p=0.009). Overall survival in FOLFIRI receiving patients with high VEGF expression was 26 months and with low VEGF expression it was 16 months (p=0.04). Median OS was not reached in the XELOX receiving patient group. FOLFIRI regime clinical benefit was 58% in high VEGF expression group whilst it was 34% in low expression group. This difference was not statistically significant but it was close to the significance threshold (p=0.06). There was no association between the therapy responses and VEGF expression of the 15 patients who received XELOX. Conclusions: There is no difference in efficacy between the first line chemotherapy regimens of the metastatic colorectal cancer. In this study, in metastatic colorectal patients with over expressed VEGF first line FOLFIRI-bevacizumab combination led to better response and survival rates.

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