G3139 (Genasense) in patients with advanced merkel cell carcinoma Journal Article
| Authors: | Shah, M. H.; Varker, K. A.; Collamore, M.; Zwiebel, J. A.; Coit, D.; Kelsen, D.; Chung, K. Y. |
| Article Title: | G3139 (Genasense) in patients with advanced merkel cell carcinoma |
| Abstract: | OBJECTIVES:: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine malignancy of the skin. Preclinical studies have identified up-regulation of the critical antiapoptosis gene bcl-2 in MCC. We conducted a multicenter phase II trial of the novel bcl-2 antisense agent (G3139, Genasense) in patients with advanced MCC. METHODS:: Twelve patients (9 men, 3 women) with histologically confirmed metastatic or regionally recurrent MCC were enrolled. Ten patients (83%) had received prior chemotherapy. Eight patients (67%) had Karnofsky performance status of 90 to 100. Patients received continuous IV infusion of G3139 (7 mg/kg/d) via central venous access in an outpatient setting for 14 days, followed by a 7-day rest period. Response was assessed at 6-week intervals. Patients were allowed to continue therapy until unacceptable toxicity or disease progression. RESULTS:: No objective responses were observed. The best response was stable disease in 3 patients and progressive disease in 9 patients. A median of 4 doses per patient (total 46 doses) was administered. Dose delays and/or reductions were required in 6 patients. One patient developed grade 4 lymphopenia. One patient developed grade 3 renal failure characterized by grade 3-elevated creatinine and grade 4 hyperkalemia. Other grade 3 events included cytopenia (n = 5), aspartate aminotransferase/alanine aminotranferease elevation (n = 3), hypophosphatemia (n = 2), and pain (n = 1). The most frequent grade 1 to 2 toxicities were elevated creatinine, ALT elevation, hypokalemia, lymphopenia, and fatigue. CONCLUSIONS:: Bcl-2 antisense therapy (G3139) was well tolerated among patients with advanced MCC. Although probable antitumor activity was documented in 1 patient, no objective responses per Response Evaluation Criteria in Solid Tumors criteria were observed. © 2009 by Lippincott Williams & Wilkins. |
| Keywords: | cancer chemotherapy; clinical article; human tissue; treatment response; clinical trial; drug tolerability; fatigue; neutropenia; advanced cancer; diarrhea; drug dose reduction; hypophosphatemia; side effect; cancer patient; outcome assessment; antineoplastic agent; anorexia; tumor localization; drug eruption; infection; multiple cycle treatment; pain; phase 2 clinical trial; anemia; leukopenia; mucosa inflammation; nausea; weight reduction; creatinine blood level; kidney failure; continuous infusion; alanine aminotransferase blood level; aspartate aminotransferase blood level; chill; dizziness; drug fever; drug hypersensitivity; hyperglycemia; lymphocytopenia; pruritus; chemotherapy induced emesis; hyperkalemia; hypoalbuminemia; hypokalemia; hyponatremia; rigor; karnofsky performance status; multicenter study; tumor recurrence; therapy delay; outpatient department; taste disorder; merkel cell carcinoma; merkel cell tumor; alkaline phosphatase blood level; corticosteroid; dyspepsia; dry skin; ataxia; oblimersen; cytopenia; antihistaminic agent; hypernatremia; hypocalcemia; bcl-2 antisense therapy; g3139; phase ii trial; diaphoresis |
| Journal Title: | American Journal of Clinical Oncology |
| Volume: | 32 |
| Issue: | 2 |
| ISSN: | 0277-3732 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2009-04-01 |
| Start Page: | 174 |
| End Page: | 179 |
| Language: | English |
| DOI: | 10.1097/COC.0b013e31817eebf8 |
| PROVIDER: | scopus |
| PUBMED: | 19307957 |
| PMCID: | PMC4311264 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: AJCOD" - "Source: Scopus" |
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