毒理性
◉ 母乳喂养期间使用总结：大多数来源认为，在母亲抗肿瘤药物治疗期间，尤其是如多柔比星等蒽环类药物，应禁忌母乳喂养。在间歇性治疗期间，可能会有一个合适的禁乳期，从而安全地进行母乳喂养；然而，由于乳汁中活性代谢物多柔比星醇含量高且持久，因此难以确定一个合适的禁乳间隔。有人建议在每次剂量后禁乳5到10天，但其他数据显示，在多柔比星50毫克/平方米的剂量后，可能需要6周的时间才能使乳汁中的水平降至安全水平。
化疗可能会不利地影响母乳的正常微生物组和化学成分。在孕期接受化疗的妇女更可能难以哺乳她们的婴儿。
◉ 对母乳喂养婴儿的影响：一名孕妇在孕27周时被诊断出患有B细胞淋巴瘤。在孕34周零4天时诱导分娩，并在产后第2天开始使用一个标准的治疗方案，包括利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松，剂量未明确，每21天一个周期。她在每个周期的前10天泵奶并丢弃，用捐赠的奶喂养婴儿，然后在下一个治疗周期之前的剩余10天进行母乳喂养。10天的禁乳期是根据大约3个长春新碱的半衰期来确定的。在完成4个周期的化疗后，她的婴儿据报道健康，没有出现任何并发症。
◉ 对泌乳和母乳的影响：一项针对在儿童恶性肿瘤期间接受化疗的青少年男性的研究发现，接受过多柔比星与血清催乳素浓度升高有关。
一名在孕中期被诊断出患有霍奇金淋巴瘤的妇女在孕晚期接受了3轮化疗，并在产后4周恢复化疗。在重新开始化疗后的16周内，在化疗前后15到30分钟收集了乳汁样本。治疗方案包括多柔比星40毫克、博来霉素16单位、长春碱9.6毫克和达卡巴嗪600毫克，所有药物在2小时内每隔2周给予一次。她的乳汁的微生物群和代谢图谱与8名未接受化疗的健康妇女进行了比较。患者的乳汁微生物群与健康妇女明显不同，Acinetobacter sp.、Xanthomonadacae和Stenotrophomonas sp.增加，而Bifidobacterium sp.和Eubacterium sp.减少。在治疗妇女的乳汁中的许多化学成分也发现了显著差异，尤其是DHA和肌醇的减少。
对74名在孕期第二或第三季度在一个中心接受癌症化疗的妇女进行了电话随访研究，以确定她们产后是否成功进行母乳喂养。只有34%的妇女能够完全母乳喂养她们的婴儿，而66%的妇女报告经历了母乳喂养困难。这与22名在孕期被诊断出患有癌症但未接受化疗的母亲91%的母乳喂养成功率相比。其他具有统计学意义的相关性包括：1.有母乳喂养困难的母亲平均接受了5.5个周期的化疗，而没有困难的母亲平均接受了3.8个周期；2.有母乳喂养困难的母亲平均在孕早期3.4周接受了第一个周期的化疗。在接受了含有多柔比星的方案的62名妇女中，有39人遇到了母乳喂养困难。
◉ Summary of Use during Lactation:Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy, especially anthracyclines such as doxorubicin. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence; however, the high levels and persistence of the active metabolite doxorubicinol in milk make defining an appropriate abstinence interval difficult. Some have suggested a breastfeeding abstinence period of 5 to 10 days after a dose, but other data suggest that it might take 6 weeks for milk levels to drop to a safe level after a dose of doxorubicin 50 mg/sq. m.
Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.
◉ Effects in Breastfed Infants:A woman was diagnosed with B-cell lymphoma at 27 weeks of pregnancy. Labor was induced at 34 4/7 weeks and treatment was begun with a standard regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in unspecified doses on a 21-day cycle, starting on day 2 postpartum. She pumped and discarded her milk and fed her infant donor milk for the first 10 days of each cycle and then breastfed her infant for the remaining 10 days before the next treatment cycle. The 10-day period of breastfeeding abstinence was determined by using about 3 half-lives of vincristine. After completion of 4 cycles of chemotherapy, her infant was reportedly healthy and developing without any complications.
◉ Effects on Lactation and Breastmilk:A study of adolescent males who had received chemotherapy for childhood malignancies found that having received doxorubicin was associated with elevated serum prolactin concentrations.
A woman diagnosed with Hodgkin's lymphoma during the second trimester of pregnancy received 3 rounds of chemotherapy during the third trimester of pregnancy and resumed chemotherapy 4 weeks postpartum. Milk samples were collected 15 to 30 minutes before and after chemotherapy for 16 weeks after restarting. The regimen consisted of doxorubicin 40 mg, bleomycin 16 units, vinblastine 9.6 mg and dacarbazine 600 mg, all given over a 2-hour period every 2 weeks. The microbial population and metabolic profile of her milk were compared to those of 8 healthy women who were not receiving chemotherapy. The breastmilk microbial population in the patient was markedly different from that of the healthy women, with increases in Acinetobacter sp., Xanthomonadacae and Stenotrophomonas sp. and decreases in Bifidobacterium sp. and Eubacterium sp. Marked differences were also found among numerous chemical components in the breastmilk of the treated woman, most notably DHA and inositol were decreased.
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 62 women who received a doxorubicin-containing regimen, 39 had breastfeeding difficulties.
来源:Drugs and Lactation Database (LactMed)
