dactinomycin
Sources réglementaires consultées
Indications approuvées
- Tumeur de Wilms, rhabdomyosarcome pédiatrique, sarcome d’Ewing, néoplasie trophoblastique gestationnelle et certaines tumeurs solides, uniquement dans les associations et protocoles autorisés.
Mises en garde cliniques
- Surveiller la numération avant chaque cycle et pendant le nadir. Ne pas administrer hors protocole oncologique spécialisé ; la myélosuppression peut provoquer une infection ou une hémorragie mortelle. — DailyMed, set_id 5da55538-2602-4704-a9da-603c9f7ff7dc
- Administrer uniquement par une voie intraveineuse perméable. Arrêter immédiatement en cas de suspicion d’extravasation : c’est un vésicant pouvant provoquer une nécrose sévère. — DailyMed, set_id 5da55538-2602-4704-a9da-603c9f7ff7dc
- Peut provoquer maladie veino-occlusive hépatique, hépatotoxicité, mucite sévère et majoration de la toxicité de la radiothérapie. Éviter les vaccins vivants pendant l’immunosuppression. — DailyMed, set_id 5da55538-2602-4704-a9da-603c9f7ff7dc
- En cas d’extravasation, arrêter, poser une nouvelle voie et appliquer glace 15 minutes quatre fois/jour pendant 3 jours ; demander avis chirurgical si la lésion progresse. — DailyMed, set_id 5da55538-2602-4704-a9da-603c9f7ff7dc
- Peut provoquer syndrome de Stevens-Johnson ou nécrolyse épidermique toxique. Arrêter définitivement si une réaction mucocutanée sévère est confirmée. — DailyMed, set_id 5da55538-2602-4704-a9da-603c9f7ff7dc
Interactions médicamenteuses
- SévèreRadiothérapie
Mécanisme: Peut majorer la toxicité tissulaire et le phénomène de rappel.
Recommandation: Avec radiothérapie concomitante, réduire la dactinomycine de 50 % et rester extrêmement prudent pendant les 2 mois suivants.
DailyMed, set_id 5da55538-2602-4704-a9da-603c9f7ff7dc
Grossesse et allaitement
Peut provoquer atteinte fœtale. Contraception féminine pendant et 6 mois après ; masculine pendant et 3 mois après. Ne pas allaiter pendant ni 14 jours après.
Bibliographie récente (PubMed)
Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy. This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy. A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decrease
Gestational trophoblastic neoplasia (GTN) is a rare form of cancer that is treated according to the World Health Organization (WHO) risk score, which predicts responsiveness to single-agent chemotherapy. Patients with WHO risk scores ≤6 have low-risk GTN, for which cure rates near 100%. Most women with low-risk GTN will respond to single-agent chemotherapy, which is given with either methotrexate or dactinomycin, and allows women to retain their fertility. This article also discusses less common treatment paradigms including second dilation and curettage and hysterectomy, as well as the emerging role of immunotherapy in managing low-risk GTN.
Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.W.I.N.G.99 and Ewing-2008 trials. We included patients with a localized high-risk disease, or pulmonary or pleural metastasis. We analysed the risk of severe toxicity according to randomised treatment group (VAI versus BuMel) and age group (<12 years, 12-17 years, 18-24 years, ≥25 years). We evaluated the heterogeneity of treatment effects by age group using interaction terms in logistic multivariable models. The analysis included 243 patients treated with VAI and 205 with BuMel. Overall, BuMel was associated with a higher risk of severe acute toxicity than VAI particularly haematological, gastrointestinal, liver, sinusoidal occlusive syndrome, and infections. Severe haematological toxicity and lower general condition were significantly more frequent in younger patients, whatever treatment. We did not observe any significant heterogeneity in terms of the excess risk of severe toxicities associated with BuMel compared to VAI according to age group. The excess of acute toxicity associated with BuMel compared to VAI does not vary significantly with age, suggesting the feasibility of BuMel across all age groups.
The authors report the prospective evaluation of reduced dose alkylator chemotherapy combined with radiotherapy for European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) standard risk nonalveolar rhabdomyosarcoma (NA-RMS). Localized node negative Intergroup Rhabdomyosarcoma Study (IRS) II/III NA-RMS at favorable sites (subgroup C), <25 years old, received five cycles of ifosfamide, vincristine, and dactinomycin (IVA) chemotherapy (30 g/m2 ifosfamide) and four cycles of vincristine and dactinomycin (if receiving radiotherapy), or nine cycles of IVA (54 g/m2 ifosfamide) ± radiotherapy. Delayed primary tumor excision was considered for IRS III tumors. The primary end points were event-free survival (EFS) and overall survival (OS). From October 2005 to December 2016, 359 evaluable patients were recruited: orbit, 164 (45.7%); head and neck nonparameningeal, 77 (21.4%); and genitourinary non-bladder/prostate, 118 (32.9%). EFS and OS were 77.4% (95% confidence interval [CI], 72.5-81.6) and 93.5% (95% CI, 90.1-95.8), respectively. Lower dose alkylator chemotherapy and radiotherapy achieved 5-year OS of 93.7% but the difference with higher dose alkylator chemotherapy +/- radiotherapy was not significant (p = 0.8003). Adjuvant radiotherapy improved EFS with 5-year estimates of 84.7% versus 65.2% for nonirradiated (p < .0001), but not OS (p = .9298). Omitting radiotherapy for orbital tumors reduced OS (5-year was 87.1% vs. 97.3% for irradiated, p = .0257). Following R0 resection (n = 60), radiotherapy did not significantly improve EFS or OS. Radiotherapy for local tumor control allows for reduction of cumulative dose of alkylators in EpSSG standard risk subgroup C RMS patients. The omission of radiotherapy did not affect OS in all patients except those with orbital RMS and was associated with inferior EFS.