Drug products: Celltop, Eposin, Eto-GRY, Etopofos, Etoposid Ebewe, Etoposid Fresenius Kabi, Etoposide Accord, Etoposide Teva, Lastet, Vepesid, Vepesid®
ATC code: L01CB01
Substances: etoposide, etoposide phosphate
Women have shown to benefit more from etoposide-based combination chemotherapy of small cell lung cancer than men. Women are more likely to develop hematological adverse events and to suffer from emesis. Etoposide should be avoided in girls and women who may become pregnant unless an effective method of contraception is used.
Generally, women mount stronger innate and adaptive immune responses than men . Women with lung cancer have a more favorable survival compared to men . The 5-year survival is 17 percent among men, and 24 percent among women in Sweden .
The incidence of lung cancer has decreased among men since from 1980s but has increased significantly among women, which reflects women's changing smoking habits. Now the proportion of smoking women is greater than the proportion of smoking men. In Sweden lung cancer made up 6.1% of all yearly cases of cancer, year 2016. The incidence was higher among women (6.8%, n=2067), compared to men (5.4%, n=1824) .Since chemotherapeutic agents share some adverse effects, evaluation of a particular agent’s sex-related adverse effects during combination chemotherapy is complicated. Another factor that complicates the evaluation of chemotherapeutic treatments’ effect is a poorer prognosis in men compared to women of most oncologic diseases that affects both sexes [4, 5]. For instance female sex is a favorable prognostic factor in small cell lung cancer . The increased risk of cancer for men has generally been explained by differences in exposure of carcinogenic factors such as smoking, alcohol consumption and exposure of harmful work-related substances [4, 5]. The belief that men might present later with more advanced cancer might in part explain the poorer prognosis seen in men .
Pharmacokinetics and dosing
According to the product summary of etoposide, although minor differences in pharmacokinetic parameters between the sexes have been observed, these are not considered to be clinically significant . A population pharmacokinetic study evaluated individual clinical covariates’ influence on pharmacokinetics parameters of etoposide in 24 patients with small cell lung cancer. Patient’s sex didn’t appear to have any influence .
A retrospective analysis of four small-cell lung cancer trials on patients (648 men, 358 women) who received similar chemotherapy consisting of cyclophosphamide-doxorubicin-vincristine and etoposide-cisplatin showed that women have increased overall response rates (80% vs 67%, respectively) and survival (median years 1.3 vs 0.91, respectively) compared with men .
A retrospective analysis of four small cell lung cancer trials on patients (648 men, 358 women) who received cyclophosphamide-doxorubicin-vincristine and etoposide-cisplatin indicated increased grade 3 and 4 hematological toxicity in women compared to men (anemia, 16% v 8%, leukopenia 80% v 69%). However, “toxic death” rates were similar for men and women (1.5% vs 1.1%, respectively). Women also had significantly more stomatitis and vomiting of all grades .Less toxicity in males with Ewing sarcoma was reported in the EURO-Ewing 99 study, in which adverse reactions to six cycles of vincristine, ifosfamide, doxorubicin, and etoposide for Ewing tumors, were evaluated in 510 males and 341 females less than 50 years old. Higher frequency of adverse reactions concerning hemoglobin and platelets were observed in females (70 %, compared to 55 % in males, on three to six cycles) .
Reproductive health issues
Etoposide like most other anti-cancer drugs is not compatible with pregnancy. Therefore, it is recommended that both men and women use contraceptives during and for at least 6 months after use of etoposide . Swedish users, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2023-01-12
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- Vera Regitz-Zagrosek. Sex and Gender Differences in Pharmacology. Springer-Verlag Berlin Heidelberg; 2012.
- Socialstyrelsen. Cancer i siffror 2018. Socialstyrelsen [www]. [updated 2018-06-10, cited 2020-10-01]. länk
- Radkiewicz, C. Sex differences in cancer risk and survival. [dissertation]. Dept of Medical Epidemiology and Biostatistics: Karolinska Institutet; 2019.
- Edgren G, Liang L, Adami HO, Chang ET. Enigmatic sex disparities in cancer incidence. Eur J Epidemiol. 2012;27(3):187-96. PubMed
- Singh S, Parulekar W, Murray N, Feld R, Evans WK, Tu D et al. Influence of sex on toxicity and treatment outcome in small-cell lung cancer. J Clin Oncol. 2005;23(4):850-6. PubMed
- Etoposide Accord (etoposid) Summary of Product Characteristics. Swedish Medical Products Agency [updated 2019-09-23, cited 2023-01-12]
- Freyer G, Tranchand B, Ligneau B, Ardiet C, Souquet PJ, Court-Fortune I et al. Population pharmacokinetics of doxorubicin, etoposide and ifosfamide in small cell lung cancer patients: results of a multicentre study. Br J Clin Pharmacol. 2000;50(4):315-24. PubMed
- Juergens C, Weston C, Lewis I, Whelan J, Paulussen M, Oberlin O et al. Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-EWING 99 clinical trial. Pediatr Blood Cancer. 2006;47(1):22-9. PubMed
- VAL-databasen. Region Stockholm. 2021 [cited 2023-01-20.] länk
Reviewed by: Diana Rydberg, Carl-Olav Stiller
Approved by: Karin Schenck-Gustafsson