Phase II trial of single agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash Journal Article
| Authors: | Schilder, R. J.; Pathak, H. B.; Lokshin, A. E.; Holloway, R. W.; Alvarez, R. D.; Aghajanian, C.; Min, H.; Devarajan, K.; Ross, E.; Drescher, C. W.; Godwin, A. K. |
| Article Title: | Phase II trial of single agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash |
| Abstract: | Objectives: Determine if cetuximab dose escalation to induce grade 2 rash correlates with anti-tumor activity and if sera-based markers could predict likelihood of response. Methods: Patients with persistent/recurrent ovarian or primary peritoneal carcinoma received an initial dose of cetuximab 400 mg/m<sup>2</sup>, then 250 mg/m<sup>2</sup> weekly for two 3-week cycles. Patients who had stable disease (SD) and < grade 2 rash were dose escalated in 75 mg/m<sup>2</sup> increments every 3 weeks until grade 2 rash or to a maximum weekly dose of 400 mg/m<sup>2</sup>. Pre- and post-treatment serum samples were evaluated for potential predictive markers of response. Results: One of 25 patients achieved partial remission (PR) and 9 patients had SD. The median progression free survival was 2.1 months; the 1-year survival rate was 54.8%. Rash (96%) was the most common drug-related adverse event. At first response assessment, 4 patients remained at 250 mg/m<sup>2</sup>; 8 patients were dose-escalated to 325 mg/m<sup>2</sup>; of these, 4 ultimately were increased to 400 mg/m<sup>2</sup>. Patients with progressive disease (PD) were removed from the study. Ninety-two serologic markers were analyzed from 20 patients to identify markers associated with clinical activity and/or predictive of outcome. Pretreatment levels of twelve markers were significantly elevated in patients exhibiting PD versus SD or PR; however, changes in marker levels during the course of treatment were not significant indicators of response. Conclusions: Single-agent cetuximab showed minimal activity in patients with recurrent ovarian cancer. Patients with elevated levels of 12 serologic markers at baseline were more likely to have earlier disease progression. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | immunohistochemistry; adult; clinical article; human tissue; protein expression; treatment response; aged; middle aged; survival rate; clinical trial; constipation; disease course; histopathology; diarrhea; drug efficacy; drug safety; monotherapy; antineoplastic agents; disease marker; disease free survival; nuclear magnetic resonance imaging; outcome assessment; ovarian cancer; ovarian neoplasms; protein blood level; apoptosis; computer assisted tomography; multiple cycle treatment; neutrophil count; phase 2 clinical trial; neoplasm recurrence, local; peritoneal neoplasms; nausea; stomatitis; drug administration schedule; epidermal growth factor receptor; interleukin 8; tumor markers, biological; creatinine; creatinine blood level; dose-response relationship, drug; proteomics; cetuximab; growth hormone; aminotransferase blood level; arthralgia; asthenia; chill; drug dose escalation; drug hypersensitivity; loading drug dose; rash; alkaline phosphatase; bilirubin; malaise; cytokine; antibodies, monoclonal; chemokine; tumor necrosis factor alpha; blood sampling; acne; ovary carcinoma; interleukin 6; remission; immunoassay; alkaline phosphatase blood level; headache; heat shock protein 27; proteinase; drug blood level; ca 125 antigen; cytokeratin 19; aminotransferase; hormone; growth factor; phase ii; infusions, intravenous; bilirubin blood level; serology; peritoneum tumor; fibrinogen; cell adhesion molecule; serum proteomics; angiogenic factor; ca 72-4 antigen; diphenhydramine; matrilysin; infusion reaction; peritoneum carcinoma; premedication; acneiform eruptions |
| Journal Title: | Gynecologic Oncology |
| Volume: | 113 |
| Issue: | 1 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2009-04-01 |
| Start Page: | 21 |
| End Page: | 27 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2008.12.003 |
| PUBMED: | 19162309 |
| PROVIDER: | scopus |
| PMCID: | PMC2741166 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 30 November 2010" - "CODEN: GYNOA" - "Source: Scopus" |
