Gonadal toxicity after combination chemotherapy for Hodgkin's disease. Comparative results of MOPP vs ABVD

Viviani, Simonetta; Santoro, Armando; Ragni, G.; Bonfante, V.; Bestetti, O; Bonadonna, Gianni

doi:10.1016/0277-5379(85)90088-4

Cited by 338 publications

(133 citation statements)

References 23 publications

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“…14 A high incidence of ovarian failure with MOPP and MVVP regimens for Hodgkin's disease, [5][6][7] but not with the ABVD regimen has been reported. 16,17 Amenorrhea is often transient in young patients and persistent in older patients after chemotherapy for Hodgkin's disease. 5 Young women treated for Hodgkin's disease may be at risk of premature menopause.…”

Section: Discussionmentioning

confidence: 99%

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Teinturier

Hartmann

Valteau‐Couanet

et al. 1998

Bone Marrow Transplant

194

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Summary:We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m 2 ) and melphalan (140 mg/m 2 ) with or without cyclophosphamide (3.6 g/m 2 ). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy. Keywords: ovarian function; high-dose chemotherapy; bone marrow transplantation; busulfan; childhood Increasing numbers of children who receive hematopoietic stem cell transplants (HSCT) for malignancies now survive. It is therefore important to evaluate ovarian toxicity secondary to the therapeutic regimens. New chemotherapy protocols will have to aim towards effecting long-term survival with minimal late morbidity. Chemotherapy is used alone or in combination with total body irradiation. Total body irradiation, used in the preparative regimens for hematologic malignancies, is deleterious to gonadal function. 1,2 Myeloablative therapy consisting of cyclophosphamide, busulfan or melphalan, has been used as an alternative to avoid the side-effects of irradiation on endocrine functions and growth. 1,3,4 Cytotoxics are known to induce ovarian toxicity in adults, dependent upon type of agent, dosage, administration schedule and patient age. 5-7 Much less is known about the effects of high-dose chemotherapy on ovarian function in children. 2,8,9 We report an analysis of ovarian function in long-term survivors following myeloablative chemotherapy and bone marrow transplantation. Patients and methodsWe screened all long-term female survivors older than 11 years who had received high-dose chemotherapy and autologous bone marrow transplantation without abdominal or pelvic radiation for malignant tumors at Institut Gustave Roussy. Twenty-one girls fulfilled these criteria.At time of transplantation, they were aged 2-17 years (median 9 years). Pubertal development was evaluated clinically according to Tanner. 10 Fourteen girls were prepubertal (stage 1), two were undergoing puberty (stage 3) and five had regular menses (stage 5). No hormonal evaluation was carried out before chemotherapy, but pubertal stages of all the patients were appropriate for their age.The study took place 1.2-13 years (median 7 years) after bone marrow transplantation and discontinuation of chemotherapy. At time of study, girls were aged 11.5-21 years (median 14.5 years).Serum concentrations of 17...

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Section: Discussionmentioning

confidence: 99%

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Teinturier

Hartmann

Valteau‐Couanet

et al. 1998

Bone Marrow Transplant

194

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“…Although these drug combinations have resulted in excellent survival rates, the majority of male patients have subsequently developed permanent azoospermia. 36,37 Mackie et al 19 studied patients with a mean age at diagnosis of 12.2 years who were treated with ChLVPP, a regimen containing both chlorambucil and procarbazine. On follow-up, 89% of these patients demonstrated severe damage to the seminiferous epithelium up to 10 years after therapy.…”

Section: The Effect Of Radiotherapy On Testicular Functionmentioning

confidence: 99%

“…19 Treatment with the ABVD regimen, which contains no alkylating agents or procarbazine, results in significantly less gonadotoxicity, with no patients demonstrating permanent azoospermia. 36 However, anthracycline exposure in this regimen renders it potentially cardiotoxic in the long term. 38 Pregnancy in High-Risk Survivors of Cancer Survivors of childhood cancer who have received radiotherapy to a field that includes their pelvis should be considered to be at high risk for uterine dysfunction in pregnancy.…”

Section: The Effect Of Radiotherapy On Testicular Functionmentioning

confidence: 99%

Oncofertility and preservation of reproductive capacity in children and young adults

Wallace

2011

Cancer

170

114

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With increasing numbers of survivors from cancer at a young age, the issue of fertility preservation has assumed greater importance. This review describes normal ovarian and testicular function and summarizes what is known about the effect of chemotherapy and radiotherapy on the gonads and uterus. All young patients with cancer or leukemia should have their fertility prognosis discussed before the initiation of treatment. Sperm and embryo cryopreservation should be considered standard practice and be widely available for those at significant risk of infertility. For prepubertal girls, ovarian tissue cryopreservation should be considered if the risk of premature menopause is high, but for the prepubertal boy there are no established techniques in current practice. Cancer 2011;117(10 suppl):2301–10. © 2011 American Cancer Society.

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“…The investigation of pituitary responsiveness to opioid stimulation can allow us to further elucidate the status of the psychoneuroendocrine system in cancer patients, in whom several neuroendocrine anomalies have been reported, including an exaggerated response of PRL to TRH in breast cancer (Willis et al, 1977;Barni et al, 1986a), as well as a paradoxical response of GH to TRH (Barni et al, 1986b), reduced LH secretion after GnRH in Hodgkin's disease (Viviani et al, 1985), and abnormally high (Raikhlin et al, 1980) or low (Pico et al, 1979) melatonin levels in various types of tumour. Because of the importance of endogenous opioid peptides in modulating neuroendocrine functions, it may be hypothesized that the anomalous endocrine responses observed in cancer patients are due to altered brain opioid activity.…”

Section: Discussionmentioning

confidence: 99%

Evidence for altered opioid activity in patients with cancer

Lissoni

Barni²,

Paolorossi³

et al. 1987

Br J Cancer

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Summary Endogenous opioid peptides have been shown to be involved in the regulation of tumour growth. At present, however, no data are available about the secretion of opioid peptides in cancer patients.To draw some preliminary conclusions on opioid brain function in human neoplasms, we evaluated hypophyseal hormone responses to the administration of a met-enkephalin analogue, There is mounting evidence indicating that endogenous opiates play a critical part in the control of immune functions (Weber & Pert, 1984). Moreover, recent experimental observations seem to demonstrate an involvement of endogenous opioid peptides in the regulation of tumour growth. As regards this hypothesis, however, the results are contradictory, since opioid substances have been seen to exert either a stimulatory (Lewis et al., 1983a, b; Simon et al., 1984) or an inhibitory role (Plotnikoff & Miller, 1983) on tumour growth, depending on the different experimental conditions. Opioid antagonists may also have stimulatory and inhibitory effects, depending on the dosage (Zagon & McLaughlin, 1983).As far as the evaluation of endogenous opioid secretion in cancer patients is concerned, no data are yet available. Preliminary results would seem to suggest an anomalous fJ-endorphin circadian rhythm in human neoplasms (Lissoni et al., 1986), the clinical significance of which remains to be determined.To further elucidate the nature of the opioid activity in human cancer, we studied the effects of a met-enkephalin analogue on the release of hypophyseal hormones in a group of patients suffering from early or advanced neoplastic disease. Materials and methodsThe study was carried out on 14 patients of both sexes (5 men, 4 premenopausal and 5 postmenopausal women), aged between 32 and 53 years (mean age 46.4 years), with histologically proven neoplastic disease. Patients were followed in the outpatient clinic of San Gerardo Hospital, Monza. Diagnosis of cancer was made for at least 4 months prior to study (4 months-5 years; mean 3.8 years). Breast cancer and lung carcinoma were the two neoplasms most frequently represented in our cases. Chronic pain was present in 2 patients only. Clinical data of cancer patients are given in Table I As controls, 12 healthy volunteers (6 men, 4 premenopausal and 2 postmenopausal women) of same age (28-51 yrs; mean 42.4) were included in the study. Volunteers were from among hospital attendants. Moreover, a second group, consisting of 7 patients (4 men, 2 premenopausal and one postmenopausal women), aged between 31 and 58 years (mean 49.3), affected by a chronic medical illness other than cancer, was evaluated. None of the patients was hospitalized during the study. The experimental protocol was explained to patients and volunteers, and informed consent was obtained.None of the cancer patients had been previously treated with oestrogens, antioestrogens or glucocorticoids. No antiemetics or other psychotropic drugs were given for at least one week prior to study. Moreover, no patient received opiates to relieve pai...

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Gonadal toxicity after combination chemotherapy for Hodgkin's disease. Comparative results of MOPP vs ABVD

Cited by 338 publications

References 23 publications

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Oncofertility and preservation of reproductive capacity in children and young adults

Evidence for altered opioid activity in patients with cancer

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