Cisplatin

An alkylating agent composed of a heavy metal derived from platinum, with antineoplastic properties due to inhibiting DNA synthesis.
Used intravenously in the treatment of advanced or metastatic cancers (ovarian, testicular, lung).

There is confusion with the elimination half-life of cisplatin. The plasma half-life of cisplatin is 20 to 30 minutes (AEMPS 2013, Bristol 2010). The compounds bound to albumin, with a high percentage of binding (> 90%), are slowly eliminated with a half-life of 4-5 days (Drugbank.com, AEMPS 2013, Bristol 2010), but these compounds do not have antineoplastic activity (AEMPS 2013) nor have they been measured in milk.

It is known from Pharmacokinetics that after 3 elimination half-lives (T½), 87.5% of the drug is eliminated from the body; 94% after 4 T½, 96.9% after 5 T½, 98.4% after 6 T½ and 99% after 7 T½. From 7 T½ the plasmatic concentrations of the drug in the body are negligible. In general, a period of at least five half-lives can be considered a safe waiting period before resuming breastfeeding (Anderson 2016).

If the half-life of the antineoplastic product is considered, it would only take 3 to 4 hours (7 half-lives) to wait before resuming breastfeeding, expressing and discarding breastmilk in the meantime.

Six different studies have analyzed the excretion of cisplatin in breastmilk (Hays 2013, Tesfaye 2013, Lanowska 2011, Ben-Baruch 1992, de Vries 1989 and Egan 1985), each with one case, except Lanowska who describes 3 cases and Tesfaye 2 cases. Cisplatin concentrations found in milk in the first 24-48 hours after administration were: 0.9 mg/L (de Vries 1989), 0.15 mg/L (Ben-Baruch 1992) and 0.2, 1,4 and 5.5 mg/L (Lanowska 2011).

The other three authors (Hays 2013, Tesfaye 2013 and Egan 1985) found concentrations in milk below the limit of detection:
- After a first administration of 70 mg of cisplatin there was a milk concentration of 0.016 mg/L at 5 hours, falling below the limit of detection after 17 hours and being totally undetectable at 66 hours, so the author (Hays 2013) believes that you can breastfeed again after waiting 3 days, having expressed and discarded breastmilk during those 72 hours.
- In two women, no detectable levels of platinum were found in the milk of either of the two (Tesfaye 2013).
- In another study (Egan 1985), after the infusion of 130 mg of cisplatin, plasma levels of the mother were rising but no detectable levels of cisplatin were found in milk in any of the multiple measurements made in the first 71 hours after infusion.

It must also be considered that its low oral bioavailability prevents its transfer to infant plasma from ingested breast milk, except in premature infants and the immediate neonatal period in which there may be increased intestinal permeability.

Due to all these findings, opinions among authors and associations are divided: those who consider that it is not prudent to breastfeed if milk levels can not be measured or until 20 days have passed after administration (Hale 2017, p.204), those who consider it better to stop breastfeeding (Pistilli 2013, WHO 2002), those who think that we must carefully weigh benefits and risks (Koren 2013), those who do not give an opinion (Moretti 2000) and those who believe that it is compatible with breastfeeding, Hays in 2013 and the American Academy of Pediatrics (AAP 2001) based on the 1985 Egas study.

Given the strong evidence that exists on the benefits of breastfeeding for the development of babies and the health of mothers, it is advisable to evaluate the risk-benefit of any maternal treatment, including chemotherapy, individually advising each mother that wishes to continue with breastfeeding (Koren 2013).