Phase II evaluation of didemnin B in advanced adenocarcinoma of the kidney

Abstract

The Southwest Oncology Group studied the response rate and toxicity of didemnin B (3.47 mg/m2 i.v. q 28 days) in patients with advanced renal cell carcinoma. There were no responses in 22 response evaluable patients. Toxicity was significant with 10 patients having grade 3 or 4 toxicity. Toxicity seen included nausea and vomiting, exacerbation of coronary artery disease, hyperglycemia, anorexia, diarrhea and hepatitis. Didemnin B was toxic but inactive in patients with renal cell treated at this dose.

Phase II trial of Didemnin B in patients with advanced renal cell carcinoma

“…The cremophorcontaining solution that Didemnin B is administered in has been suggested as a possible causative factor for allergic reactions rather than the drug itself [2]. Taylor et al [4] have reported 0/22 response to Didemnin B in patients with renal cell cancer and 3 acute drug reactions. The observed toxicity of anaphylaxis warrents caution for consideration of clinical trials with Didemnin B for other malignancies.…”

Cardiac Glycosides Induce Cell Death in Human Cells by Inhibiting General Protein Synthesis

“…As general protein synthesis inhibitors have not proven useful as cancer therapeutics, it is highly unlikely that the effects of CGs on protein synthesis can be successfully exploited to treat cancer [25], [26], [27], [28], [29], [30]. Furthermore, the narrow therapeutic window of CGs indicates that the serum levels required to achieve protein synthesis inhibition could cause intoxication.…”

“…Using this unbiased approach we unexpectedly discovered that CGs are potent general protein synthesis inhibitors in a variety of normal and transformed human cells. Whereas drugs such as sirolimus (rapamycin) that inhibit the translation of a specific subset of mRNAs are now used to treat certain neoplasms, the general protein synthesis inhibitors have proven to be very toxic and not useful in the treatment of cancer [25], [26], [27], [28], [29], [30]. Therefore, our findings have direct implications for the validity of CGs as promising cancer drugs and discourage further clinical testing of cardiac glycosides or their derivatives as anti-cancer agents.…”

Macrocyclic N-Methylated Cyclic Peptides and Depsipeptides

“…One partial response was achieved (5%) in 21 patients [193]. Some phase II clinical trials were also undertaken by other groups [122,[195][196][197][198][199][200][201][202][203]. From the data analysis, didemnin B 176 is not recommended in the treatment of renal cell carcinoma.…”