Summary of Use during Lactation

Most sources consider that mothers receiving antineoplastic therapy should not breastfeed, especially with alkylating agents such as cisplatin.[1] Excretion of platinum into milk occurs, but results from case reports are inconsistent. Platinum in milk may increase with repeated courses of chemotherapy. The exact form(s), and toxicity of platinum excreted into breastmilk are also not known. The nursing infant would receive platinum compounds orally rather than intravenously and oral absorption of platinum compounds by infants is not known. It appears that it is not safe to breastfeed after cisplatin chemotherapy, and breastfeeding should probably be discontinued.

Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[2] Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.

Drug Levels

Maternal Levels. Platinum was not detected (<100 mcg/L) in the milk of one patient at any time after an IV infusion of 100 mg/sq. m (130 mg) of cisplatin.[3]

In another patient, trough milk platinum was 900 mcg/L at 19.5 hours after her second daily dose of cisplatin 20 mg/sq. m infused intravenously over 4 hours. The simultaneous plasma platinum level was 800 mcg/L.[4] Note: the original report stated a cisplatin dose of 30 mg/sq. m, but this was later corrected to 20 mg/sq. m in a published erratum.

A patient was given cisplatin 60 mg/sq. m (100 mg) infused intravenously over 3 hours. Samples from two cycles of therapy found average peak milk platinum concentrations of about 125 mcg/L occurred at 30 minutes after the dose and about 112 mcg/L at 18 hours after the dose. Milk platinum levels were about 10% of simultaneous plasma levels at all time points over the 18-hour sampling periods of two cycles.[5]

Three patients with cervical cancer received cisplatin 20 mg/sq. m during pregnancy as part of their treatment. All women had a cesarean section and hysterectomy between 31 and 35 weeks of gestation, followed by another course of chemotherapy. Breastmilk samples "in the first days of lactation" were obtained and analyzed, although the time since the last cisplatin dose and the time since surgery were not specified. Cisplatin concentrations in breastmilk samples were 0.2, 1.4, and 5.5 mg/L, which were 0.9%, 2.3% and 9% of concentrations in maternal blood at the time of surgery.[6]

Two women were treated with unspecified doses of cisplatin for treatment of cervical cancer every 2 weeks during pregnancy. The time of the last dose before delivery was not clearly specified in the abstract. Breastmilk samples were obtained daily on days 1 to 4 postpartum. Cisplatin was measured by flameless atomic absorption spectrophotometry. Platinum was undetectable (lower limit of assay not specified) in all of the samples.[7]

A woman was given her first dose of 70 mg (40 mg/sq. m) of cisplatin intravenously at 6 weeks postpartum for treatment of cervical cancer discovered during pregnancy. Fifteen milk samples were obtained between 4 and 70 hours after the dose. Total platinum was measured in milk. The first sample at 4.25 hours after the dose contained about 16 mcg/L of platinum. Concentrations fell with a half-life of 10.2 hours until 17 hours after the dose. Between 17 and 57 hours after the dose, platinum was detectable (>2.5 mcg/L), but not quantifiable (<5 mcg/L) in milk. Platinum was undetectable (<2.5 mcg/L) at 66 and 70 hours after the dose. The authors estimated that a breastfed infant would be exposed systemically to between 0.08 and 0.12% of a therapeutic dose and that resumption of breastfeeding would be possible at 72 hours after a dose of this size.[8]

A breastfeeding woman was started on cisplatin 70 mg intravenously once a week for 3 weeks for invasive squamous cell carcinoma at 5 months postpartum. She pumped her milk 3 to 4 times daily and discarded it for the first 5 days after each dose and continued to collect milk for several months. Platinum elimination from milk was biphasic. A milk total platinum concentration of about 7 mcg/L was found on day 11. The concentration decreased to 0.6. mcg/L on day 96 and then increased again by day 129 to about 5 mcg/L. Platinum was detectable in milk for at least 159 days after the first dose.[9]

A postpartum patient was diagnosed with an ovarian germ cell tumor. Her treatment consisted of 4 cycles of BEP (bleomycin, etoposide on day 1 and cisplatin 90 mg on days 1 and 2), with the cycle repeated every 21 days. Using an electric pump, she collected 98 complete 24-hour samples of breastmilk after chemotherapy that were analyzed for platinum. Reported cisplatin concentrations in the milk samples were calculated based on the measured platinum concentrations using the molecular weight of cisplatin with the assumption that all measured platinum was cisplatin. Peak milk levels after the first round of chemotherapy were about 44 mcg/L; peak levels increased to about 46 mcg/L after the second round and to about 62 mcg/L in the fourth round. After 4 rounds of chemotherapy, milk platinum levels remained elevated for more than 10 days. The authors calculated the time for the milk concentration to reach a relative infant dosage (RID) level below 1% to be 14 days after the third cycle; however, the actual platinum species in milk were not determined.[10]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Two women were treated with unspecified doses of cisplatin for treatment of cervical cancer every 2 weeks during pregnancy. They both breastfed their newborn infants. Follow-up examinations of the infants, including Bayley scale test, neurology, and echocardiography at age of 20 and 35 months revealed normal findings.[7]

Effects on Lactation and Breastmilk

A study of adolescent males who had received chemotherapy for childhood malignancies found that having received cisplatin was associated with elevated serum prolactin concentrations.[11] Another study of survivors of testicular cancer found that about 6% of those treated with cisplatin had abnormally high prolactin levels and 2% had abnormally low prolactin levels.[12]

A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 3 women who received a cisplatin-containing regimen, 1 had breastfeeding difficulties.[13]

References

1.

Pistilli B, Bellettini G, Giovannetti E, et al. Chemotherapy, targeted agents, antiemetics and growth-factors in human milk: How should we counsel cancer patients about breastfeeding? Cancer Treat Rev 2013;39:207-11. [PubMed: 23199900]

2.

Urbaniak C, McMillan A, Angelini M, et al. Effect of chemotherapy on the microbiota and metabolome of human milk, a case report. Microbiome 2014;2:24. [PMC free article: PMC4109383] [PubMed: 25061513]

3.

Egan PC, Costanza ME, Dodion P, et al. Doxorubicin and cisplatin excretion into human milk. Cancer Treat Rep 1985;69:1387-9. [PubMed: 4075315]

4.

de Vries EG, van der Zee AG, Uges DR, et al. Excretion of platinum into breast milk. Lancet 1989;1:497. [PubMed: 2563865]

5.

Ben-Baruch G, Menczer J, Goshen R, et al. Cisplatin excretion in human milk. J Natl Cancer Inst 1992;84:451-2. [PubMed: 1538424]

6.

Lanowska M, Kohler C, Oppelt P, et al. Addressing concerns about cisplatin application during pregnancy. J Perinat Med 2011;39:279-85. [PubMed: 21391877]

7.

Tesfaye H, Halaska MJ, Branova P, et al. Breast-fed infants whose mothers were on platinum based chemotherapy: Cases with promising outcomes. Ther Drug Monit 2013;35:693. doi:10.1097/FTD.0b013e3182a8ef2b [CrossRef]

8.

Hays KE, Ryu RJ, Swisher EM, et al. Duration of cisplatin excretion in breast milk. J Hum Lact 2013;29:469-72. [PMC free article: PMC4041270] [PubMed: 23492761]

9.

Canale S, Duffy J, Chang CH, et al. Prolonged excretion of platinum in human breast milk after cisplatin therapy. Clin Lact 2019;10:183-7. doi:10.1891/2158-0782.10.4.183 [CrossRef]

10.

Damoiseaux D, Calpe S, Rosing H, et al. Presence of 5 chemotherapeutic drugs in breast milk as a guide for the safe use of chemotherapy during breastfeeding: Results from a case series. Clin Pharmacol Ther 2022;112:404-10. [PubMed: 35486426]

11.

Siimes MA, Ropponen P, Aalberg V, et al. Prolactinemia in adolescent males surviving malignancies in childhood: Impaired dating activity. J Adolesc Health 1993;14:543-7. [PubMed: 8312290]

12.

Wiechno P, Demkow T, Kubiak K, et al. The quality of life and hormonal disturbances in testicular cancer survivors in cisplatin era. Eur Urol 2007;52:1448-54. [PubMed: 17544206]

13.

Stopenski S, Aslam A, Zhang X, et al. After chemotherapy treatment for maternal cancer during pregnancy, is breastfeeding possible? Breastfeed Med 2017;12:91-7. [PubMed: 28170295]

Substance Name

Cisplatin

CAS Registry Number

15663-27-1

Drug Class

Breast Feeding

Lactation

Milk, Human

Antineoplastic Agents

Platinum Compounds