Chlorambucil
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| ID | DRUG-CHLORAMBUCIL |
|---|---|
| Tipo | Fármaco |
| Alegais | CB-1348LeukeranХлорамбуцил |
| Estado | reviewed 2026-04-27 | pending_clinical_signoff |
| Doenças | DIS-CLL |
| Fontes | SRC-ESMO-CLL-2024 SRC-NCCN-BCELL-2025 |
Fatos sobre as drogas
| Classe | Agente alquilante — mostarda de azoto |
|---|---|
| Mecanismo | Bifunctional alkylating agent of the nitrogen-mustard class. Aromatic nitrogen mustard with a phenylbutyric-acid carrier; less reactive (and therefore better orally bioavailable + less acutely toxic) than classical nitrogen mustards. Forms aziridinium intermediates that alkylate the N7 position of guanine, generating intra- and interstrand DNA cross-links → blocked replication, transcription, and apoptosis (preferentially in slowly-dividing lymphoid cells). Cell-cycle non-specific. Used for decades in CLL (now largely supplanted by BTK and BCL2 inhibitors), Waldenström, and as the partner of obinutuzumab in elderly comorbid CLL (CLL11 trial). |
| Dose típica | CLL11 (obinutuzumab + chlorambucil, elderly comorbid CLL 1L): 0.5 mg/kg PO on days 1 and 15 of each 28-day cycle × 6 cycles. Monotherapy CLL (historical): 0.1-0.2 mg/kg PO daily continuous OR 0.4 mg/kg PO every 2 weeks (escalate by 0.1 mg/kg until response or myelosuppression). Waldenström: 0.1 mg/kg PO daily until best response. Take on empty stomach (food reduces bioavailability ~10-20%). |
| Ucrânia registada | Verdade |
| NSZU reembolsado | Verdade |
| Ucrânia verificada pela última vez | 2026-04-27 |
Avisos
- Secondary malignancies — therapy-related AML / MDS (cumulative dose >0.4 g/m² substantially increases risk; latency 4-7 years)
- Mielossupressão grave + prolongada (especialmente cumulativa; recuperação pode levar semanas- meses)
- Infertilidade (azoospermia, insuficiência ovárica — muitas vezes permanente; conselhos sobre a preservação da fertilidade antes do tratamento)
- Mutagenicidade / carcinogenicidades (genotóxico; risco de cancro a longo prazo)
Notas
CLL11 (Goede 2014, NEJM): obinutuzumab + chlorambucil vs rituximab + chlorambucil vs chlorambucil alone in previously-untreated CLL with comorbidities (CIRS >6 OR CrCl 30-69) — mPFS 26.7 vs 15.2 vs 11.1 mo. Established G-Clb as a fitness-tailored 1L for elderly comorbid CLL. Now positioned behind venetoclax-obinutuzumab and BTK-inhibitor monotherapy in most NCCN/ESMO algorithms, but remains relevant for patients without access to those agents OR with contraindications to them. Long history (since 1957) — most familiar oral chemotherapy in community haematology. Counsel on infertility and secondary-malignancy risk before initiating; consider sperm banking / oocyte cryopreservation for younger patients (uncommonly used in this age group). TLS prophylaxis (allopurinol + hydration) for high-burden disease at cycle 1.
Usado por
Indicação
IND-CLL-ELDERLY-O-CHL- IND-CLL-ELDERLY-O-CHL
Esquema terapêutico
REG-O-CHL- Obinutuzumab + Chlorambucil (G-Clb, CLL11 — idosos comorbidos CLL 1L)