Association between cumulative cisplatin dose and reproductive and sexual functions in patients with malignant ovarian germ cell tumors treated with bleomycin, etoposide, and cisplatin therapy: a case series study

Abstract

Background: The impact of cumulative dose of cisplatin on gonadal function has not been clarified. We evaluated whether the cumulative cisplatin dose affects the resumption of menses in patients treated with bleomycin, etoposide, and cisplatin (BEP).

Main body: A case series study of women < 40 years with malignant ovarian germ cell tumors receiving BEP was conducted at Mie University Hospital. Using linear regression analysis, the correlation between the cumulative dose and resumption of menses was determined. Additionally, we compared the resumption of menses stratified by age (age < 20 years or ≥ 20 years). Ten women (median age: 20 [interquartile range: 15-26] years) have received a median of 4 cycles of BEP. The median period of resumption of menses was 5 months, which had no correlation with cumulative doses of bleomycin (143 mg/m² [71-220], y = -0.0069 x + 6.15, r = 0.19, P = 0.60), etoposide (1,533 mg/m² [900-2,000], y = 0.0004 x + 4.56, r = 0.08, P = 0.82), and cisplatin (363 mg/m² [225-400], y = 0.01 x + 1.67, r = 0.35, P = 0.32). Although the resumption of menses was comparable across ages, the cumulative doses of cisplatin were higher in patients aged < 20 years than in those aged ≥ 20 years (400 mg/m² [363-450] vs. 225 mg/m² [225-350], P = 0.02). Similarly, patients aged < 20 years had a higher cumulative etoposide dose than those aged ≥ 20 years (2,000 mg/m² [1,533-2,250] vs. 900 mg/m²[900-1,600], P = 0.03). Moreover, patients aged < 20 years received more cycles of BEP than those aged ≥ 20 years (4 cycles vs. 3 cycles, P = 0.03).

Short conclusion: All patients can recover menses after BEP, and the resumption of menses appeared at the median period of 5 months after BEP. The timing of menses resumption did not correlate with the cumulative doses of cisplatin.

Keywords: Cancer; Cisplatin; Fertility; Malignant ovarian germ cell tumor.

Fig. 1

Association between cumulative doses of anticancer drugs and timing of resumption of menses. The X-axis and Y-axis represent the cumulative bleomycin (a), etoposide (b), and cisplatin (c) dose and the timing of resumption of menses, respectively. Open circles represent age < 20 years. Closed circles represent age ≥ 20 years. Gray points represent duplicated points (age 18 and 27 years). a: This point is duplicated in two patients (aged 22 years and 29 years). b: This point corresponds to a patient treated with vinblastine, actinomycin D, and cyclophosphamide (VAC) in addition to bleomycin, etoposide, and cisplatin (BEP)