157P - Survey of the onset of the dose limiting toxicity in oncology phase I trial: How long should we assess the toxicity profiles in the era of molecula...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Clinical research
Presenter Noriko Kobayashi
Citation Annals of Oncology (2016) 27 (suppl_9): ix46-ix51. 10.1093/annonc/mdw579
Authors N. Yamamoto1, N. Kobayashi2
  • 1Department Of Thoracic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2Clinical Research Coordinator Section, Center For Research Administration, National Cancer Center Hospital, 104-0045 - Tokyo/JP

Abstract

Background

The mainstream of the development of anticancer drugs has changed from cytotoxic drugs to molecularly targeted drugs. The development of immunotherapy has also increased since 2009. The dose-limiting toxicity (DLT) in phase I trials is usually evaluated during the first cycle of therapy such as grade 3 ≥ non-hematological and grade 4 ≥ hematological toxicities. The chronic toxicities after 1st cycle of treatment are often required to be evaluated in the molecular targeted drugs, but the period of DLT evaluation has still been conservative in phase I trials. We explored the favorable assessment period of acute and chronic toxicities of the single-agent molecular targeted drugs in phase I trials.

Methods

We retrospectively surveyed the consecutive cases in phase I trials of the single-agent molecularly targeted drugs in our hospital.

Results

From August 1996 to December 2014, a total of 780 patients were enrolled in phase I trials of the single-agent molecular targeted drugs. Median age was 66 years (range 25-94). DLT and the toxicities equivalent to DLT were observed in 66 patients. As acute toxicities, 88 grade 3 or more non-hematological, and 10 grade 4 hematological toxicities were observed. As for chronic toxicities, 12 grade 3 or more non-hematological toxicities were observed. However, no grade 4 hematological toxicities were observed as chronic toxicity. Grade 3 or more chronic non-hematological toxicities without acute toxicities were observed in 8 patients.

Conclusions

In the molecular targeted drugs in phase I trials, the toxicities equivalent to DLT were mainly non-hematological and frequently observed in the chronic phase (i.e., after the 1st cycle). We need to establish the optimal evaluation period of DLT or equivalent toxicities for the molecular targeted drugs in phase I trials. Also, we need to translate this period for the toxicity evaluation of the immuno-therapeutic drugs that are increasing in development.

Clinical trial indentification

Legal entity responsible for the study

National Cancer Center Hospital

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.