Phase I trial to determine the safety of a new anti-cancer drug: PD 0332991

This article presents the results from the first human trial of PD 0332991, a new anti-cancer drug. The main objective of the study was to determine the safety and recommended dose for further testing. Results warrant further studies and revealed that neutropenia (low white cell count) was the main side effect.

Cells multiply by dividing themselves. CDK proteins are involved in controlling this cell division process. Some CDK proteins, notably CDK 4 and 6 found in cancer cells, can be blocked with highly specific drugs that may stop tumor growth.

PD 0332991 is currently investigated as a clinically useful CDK 4/6 blocker (inhibitor). Previous trials showed that it inhibits tumor growth in mice and that it may be used together with other chemotherapy drugs to lower toxicity.

The study presented in this article was the first human trial of PD 0332991. 41 patients previously treated with other types of chemotherapy were included between 2004 – 2008. The main objective was to discover the maximum tolerated dose of the drug that may be used in subsequent trials. Results showed that a dose of 125 mg/m² of PD 0332991, given daily in the first 21 days out of 28 (which represented a full cycle) was safe. The main adverse effect, that required stopping the drug, was neutropenia (low white cell count). Other adverse effects were: fatigue, nausea and diarrhea.

The authors recommended further testing (Phase II trials) with a 125 mg/m² dose of PD 0332991.

Despite showing significant promise, CDK 4/6 inhibitors still need thorough testing before becoming a standard of care. This was the first human trial of PD 0332991 and the drug was only given to a small number of patients with advanced disease.

Results from Phase II trials have not yet been officially published, but early reports quote a progression-free survival (time before cancer progression) of 26.1 months in breast cancer patients given PD 0332991 and Letrozole (Femara – a hormonal treatment for breast cancer) compared to 7.5 months with Letrozole alone.  In light of encouraging results, further studies are planned for 2013.