July 15 Clinical Cancer Research Highlights

PDF Version for Printing

Selected Articles from the July 15, 2007 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the July 15 issue of Clinical Cancer Research.

---

High TIMP-1 Levels Predict Poor Response
in Colorectal Cancer

Sørensen et al.
Page 4117

Tumor and plasma TIMP-1 is upregulated in colorectal cancer (CRC). In vitro studies have shown that TIMP-1 protects cancer cells against chemotherapy induced apoptosis. Based on these observations, Sørensen and associates hypothesized that metastatic CRC patients with high plasma levels of TIMP-1 would be less sensitive to apoptosis-inducing chemotherapy. The hypothesis was tested in a cohort of 90 patients with metastatic CRC treated with 5-fluorouracil, leucovorin, and irinotecan. The objective response rate was significantly lower in patients with high levels of plasma TIMP-1. Patients with high plasma TIMP-1 levels also had a significantly shorter survival rate.

---

Accelerator Mass Spectrometry Useful
to Evaluate Resistance

Boddy et al.
Page 4164

Imatinib has transformed the treatment of chronic myeloid leukemia. A number of patients, however, have recurrent, imatinib-resistant disease during therapy. Some element of imatinib resistance may have a pharmacological mechanism. As a potential tool to investigate the pharmacokinetics and metabolism of imatinib in patients on chronic therapy, Boddy and colleagues used a microdose of ¹⁴C-labelled imatinib, making use of accelerator mass spectrometry (AMS) to measure plasma concentrations. Comparison of AMS data with conventional LCMS analysis indicated a broad degree of agreement, but with some variation within individual patients. This feasibility study showed that AMS could be a useful tool to investigate pharma­cological mechanisms of resistance.

---

Vaccine Induces Antibodies in Ovarian Cancers

Sabbatini et al.
Page 4170

The current standard treatment for patients with advanced ovarian cancer consists of aggressive surgical cytoreduction followed by taxane-and platinum-based chemotherapy. Although the overall survival rate has increased to 65.6 months, less than 30% of patients will remain free of disease. Preclinical models have shown the clearance of circulating tumor cells and the elimination of systemic micrometastasis through the use of both passively administered and vaccine-induced antibodies. Sabbatini and colleagues characterized the safety and immunogenicity of a heptavalent antigen-KLH plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in complete clinical remission. The heptavalent-KLH conjugate plus QS21 vaccine safely induced antibody responses against 5 of 7 antigens, warranting further clinical investigation.

---

Patupilone/Carboplatin Combination is Well Tolerated

Forster et al.
Page 4178

Patupilone is a microtubule-targeting chemotherapeutic agent with clinical activity in a broad range of taxane-sensitive/
resistant tumor types. Forster and colleagues examined the safety, tolerability and pharmacokinetics of patupilone in combination with carboplatin in patients with advanced solid tumors. Of 37 patients enrolled, the majority previously received taxanes (81%) and/or platinum-containing drugs (97.3%). The maximum tolerated dose of patupilone with carboplatin AUC 6 was 4.8 mg/m2; The combination of patupilone 4.8 mg/m2/carboplatin AUC 6 was well tolerated and showed antitumor activity similar to established regimens in patients with recurrent platinum-­sensitive ovarian cancer. The optimal dose for this regimen is being further refined in phase II trials.

---