This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nasti, G. Articles by Delrio, P. Search for Related Content PubMed PubMed Citation Articles by Nasti, G. Articles by Delrio, P. Social Bookmarking                            What's this?

Trials on Preoperative Chemotherapy in Resectable Colorectal Liver Metastases Need Prospective Evaluation of Predictive Factors of Response

Department of Colorectal Oncology/Medical Oncology, National Cancer Institute, G. Pascale Foundation, Naples, Italy

Massimiliano Berretta

Department of Medical Oncology A, National Cancer Institute, Aviano, Italy

Paolo Delrio

Department of Colorectal Oncology/Surgical Unit, National Cancer Institute of Naples, G. Pascale Foundation, Naples, Italy

To the Editor:

We read with interest the recent article by Gruenberger et al¹ on the feasibility of bevacizumab, capecitabine, and oxaliplatin as preoperative treatment in patients with resectable liver metastases. Six cycles of treatment were administered, and the sixth did not include bevacizumab (median, six cycles; standard deviation, ± 1.41). Three of 56 patients experienced progression (5.4%) and 12 had stable disease (21.4%) before surgery. Even if feasible, the lack of response in greater than 25% of patients in this treatment setting should be critically considered. In fact, both the lack of surgical intervention in those patients experiencing progression and the well-known chemotherapy toxicity in patients with stable disease could be detrimental for quality of life and survival. For this reason we would like to stress the urgent need for predictive factors which would improve selection of patients with resectable disease as candidates for preoperative treatment. This issue is rarely evaluated in prospective trials of preoperative chemotherapy.

In this regard, two easily assessable factors should be of interest: initial size of liver metastases and changes of tumor glucose uptake of liver metastases after few cycles of chemotherapy. Size of liver metastases could be a critical issue when bevacizumab is added in preoperative treatments. In fact, bevacizumab is unlikely to act on large tumors where the hypoxia status and the blood supply are less dependent on vascular endothelial growth factor pathway.^2,3 It would be interesting to know if there was a correlation between large dimensions of metastases and lack of response to the therapy.

Tumor glucose uptake evaluation after few cycles of preoperative chemotherapy could help to select those patients with unresponsive disease avoid administration of ineffective treatment.⁴ In this regard, we are now conducting a prospective trial of neoadjuvant chemotherapy in resectable liver metastases with the aim of evaluating the predictive role of positron emission tomography after one cycle of chemotherapy; preliminary data suggest a possible correlation between positron emission tomography negativization (positive result before and negative result on subsequent imaging) and response to chemotherapy. We would be interested to know the authors’ opinion in this regard and if they have evaluated these or other predictive factors in their study.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Gruenberger B, Tamandl D, Schueller J, et al: Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol 26:1830-1835, 2008[Abstract/Free Full Text]

2. Gerber HP, Ferrara N: Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res 65:671-680, 2005[Abstract/Free Full Text]

3. Hicklin DJ, Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23:1011-1027, 2005[Abstract/Free Full Text]

4. Goshen E, Davidson T, Zwas ST, et al: PET/CT in the evaluation of response to treatment of liver metastases from colorectal cancer with bevacizumab and irinotecan. Technol Cancer Res Treat 5:37-43, 2006[Medline]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nasti, G. Articles by Delrio, P. Search for Related Content PubMed PubMed Citation Articles by Nasti, G. Articles by Delrio, P. Social Bookmarking                            What's this?