Database creation on the feasibility of galenic modification of oral anticancer drugs

Introduction
Oral anticancer drugs (OADs) are increasingly being commercialized. Patients suffering from swallowing disorders (SD) (before or during therapy instauration), require adaptation of the galenic form to the oral liquid form in order to preserve the therapeutic line since many targeted therapy are only proposed as solid oral form. OADs are considered a priori to be carcinogenic, mutagenic and/or reprotoxic (CMR), which leads to a galenic formulation that can’t be modified without equipment to protect the environment. The objective of our work was to take stock of the galenic alternatives available of OADs for patients with SD by creating a database to provide standardised, safe and quick answer.

Materials and methods
For each drug commercialized available in our hospital, availability of marketed adapted galenic form was searched. In absence, the following information was collated on the basis of industrial (considered as the most relevant) and literature data : CMR properties, possibility of galenic modification (daily extemporaneously or magistral preparation if stability data), compatibility with nasogastric tube (NGT) and bioequivalence. In addition, NGT obstruction and preparation feasibility (dissolution condition) tests were carried out to complete the database. If therapeutic drug monitoring (TDM) was relevant, the feasibility and location of the analysis was established.
OADs were classified in 5 categories: marketed galenic alternative, deconditioning by the hospital pharmacy (opening capsules or crushing tablets under a safety cabinet at the pharmacy then for a safe extemporaneously reconstitution in the ward, extemporaneously galenic modification possible in the ward suspension in the ward (tablets/capsules disintegrate in water), referenced magistral preparation (stability data), or no galenic alternative.

Results
Among 70 OADs identified, all were CMR and 12 had a suitable galenic available. Among the 58 remaining drugs, nine had guidelines for deconditioning, 27 were able to be extemporaneously modified in the ward, 12 were eligible for a magistral preparation with stability data up to 10 days, and 10 presenting no galenic alternative. For all the OADs no data on adsorption were found, but tube passage testing showed that none of them obstructed it. A TDM is possible for 49 drugs.

Conclusion
For 83% of OADs available on our site, we offer a suitable galenic adaptation for hospitalized patients (in absence of marketed form). As few data are available to ensure the impact of galenic modification on pharmacokinetic, TDM is highly recommended which is possible for 70% of OADs. This database allows us to provide an immediate response to the clinician, to give the patient access to therapeutic despite his SD, and ensure that nurses aren’t exposed to toxic agents. However, the feasibility of pursuing this alternative at home must be discussed with the physician.

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