procarbazine
Regulatory sources consulted
Approved indications
- In adults, in combination with other antineoplastic agents for Hodgkin lymphoma; it is also used for advanced lymphomas and brain tumors within oncology protocols.
- In children and adolescents aged 2–18 years, in combination treatment for Hodgkin lymphoma.
Contraindications
Absolute
- Hypersensitivity to procarbazine.
- Inadequate marrow reserve or severe leukopenia, thrombocytopenia, or anemia.
- Severe renal or hepatic impairment.
- Pregnancy.
- Breastfeeding.
Clinical warnings
- Boxed warning · It must be administered under the supervision of a clinician experienced with antineoplastic drugs and with adequate clinical and laboratory monitoring available. — DailyMed, MATULANE set_id 1aa75a3a-18c9-49e1-91a6-293d0b7da756
- Major warning · Check blood counts and kidney and liver function before each cycle; during treatment, check blood counts at least twice weekly or every 3–4 days and kidney and liver function weekly. — AEMPS CIMA, NATULAN 50 mg, registro 42248
- Major warning · Withhold for significant cytopenias, neurologic symptoms, hypersensitivity, diarrhea, stomatitis, or persistent vomiting. Tremor, coma, and seizures have been reported in pediatric patients. — AEMPS CIMA, NATULAN 50 mg, registro 42248
- Major warning · It is mutagenic and can cause infertility, permanent azoospermia, acute myeloid leukemia, and other secondary cancers. Consider fertility preservation before treatment. — AEMPS CIMA, NATULAN 50 mg, registro 42248
- Major warning · Procarbazine acts as a weak monoamine oxidase inhibitor. Avoid tyramine-rich foods, alcohol, and sympathomimetics to reduce hypertensive crises and other severe reactions. — AEMPS CIMA, NATULAN 50 mg, registro 42248
Drug interactions
- HighTyramine-rich foods
Mechanism: Weak monoamine oxidase inhibition can precipitate a hypertensive reaction.
Recommendation: Avoid aged cheeses, yeast extracts, and other tyramine-rich foods during treatment.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- HighAlcohol
Mechanism: It can cause a disulfiram-like reaction and increase central nervous system depression.
Recommendation: Do not drink alcohol during treatment.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- HighSympathomimetics and decongestants
Mechanism: Monoamine oxidase inhibition can increase the pressor response.
Recommendation: Avoid the combination, including over-the-counter products.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- HighCentral nervous system depressants, anticholinergics, tricyclics, and phenothiazines
Mechanism: It can increase sedation, hypotension, and anticholinergic effects.
Recommendation: Avoid or reduce the dose with specialist monitoring.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- ModerateEnzyme-inducing antiepileptic drugs
Mechanism: A higher frequency of hypersensitivity reactions has been observed.
Recommendation: Prefer a non-inducing antiepileptic when possible.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- HighLive vaccines
Mechanism: Immunosuppression increases the risk of generalized vaccine infection.
Recommendation: Avoid during immunosuppressive treatment.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
Adverse events
Common (≥1%)
infections · leukopenia · thrombocytopenia · anemia · anorexia · nausea · vomiting · alopecia
Rare but serious
acute myeloid leukemia or myelodysplastic syndrome · pancytopenia or marrow aplasia · anaphylaxis or angioedema · seizures or coma · interstitial lung disease · severe hepatotoxicity · Stevens-Johnson syndrome or toxic epidermal necrolysis
Pregnancy and lactation
It is contraindicated during pregnancy because of fetotoxicity and malformation risk, especially in the first trimester. Use adequate contraception during treatment and for 6 months afterward in females and 3 months afterward in males. It can cause permanent infertility; consider cryopreservation. Do not breastfeed during treatment.
Recent literature (PubMed)
Malignant primary brain tumors cause more than 15 000 deaths per year in the United States. The annual incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals and increases with age. Five-year survival is approximately 36%. Approximately 49% of malignant brain tumors are glioblastomas, and 30% are diffusely infiltrating lower-grade gliomas. Other malignant brain tumors include primary central nervous system (CNS) lymphoma (7%) and malignant forms of ependymomas (3%) and meningiomas (2%). Symptoms of malignant brain tumors include headache (50%), seizures (20%-50%), neurocognitive impairment (30%-40%), and focal neurologic deficits (10%-40%). Magnetic resonance imaging before and after a gadolinium-based contrast agent is the preferred imaging modality for evaluating brain tumors. Diagnosis requires tumor biopsy with consideration of histopathological and molecular characteristics. Treatment varies by tumor type and often includes a combination of surgery, chemotherapy, and radiation. For patients with glioblastoma, the combination of temozolomide with radiotherapy improved survival when compared with radiotherapy alone (2-year survival, 27.2% vs 10.9%; 5-year survival, 9.8% vs 1.9%; hazard ratio [HR], 0.6 [95% CI, 0.5-0.7]; P < .001). In patients with anaplastic oligodendroglial tumors with 1p/19q codeletion, probable 20-year overall survival following radiotherapy without vs with the combination of procarbazine, lomustine, and vincristine was 13.6% vs 37.1% (80 patients; HR, 0.60 [95% CI, 0.35-1.03]; P = .06) in the EORTC 26951 trial and 14.9% vs 37% in the RTOG 9402 trial (125 patients; HR, 0.61 [95% CI, 0.40-0.94]; P = .02). Treatment of primary CNS lymphoma includes high-dose methotrexate-containing regimens, followed by consolidation therapy with myeloablative chemotherapy and autologous stem cell rescue, nonmyeloablative chemotherapy regimens, or whole brain radiation. The incidence of primary malignant brain tumors is approximat
Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles. This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1-3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1-7), and prednisone (40 mg/m2 orally on days 1-14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalT
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
To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults. ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature. Fifty-nine randomized trials focusing on therapeutic management were identified. Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMT promoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines.
Anaplastic oligodendrogliomas are a type of glioma that occurs primarily in adults but are also found in children. These tumors are genetically defined according to the mutations they harbor. Grade II and grade III tumors can be differentiated most of the times by the presence of anaplastic features. The earliest regimen used for the treatment of these tumors was procarbazine, lomustine, and vincristine. The treatment modalities have shifted over time, and recent studies are considering immunotherapy as an option as well. This review assesses the latest management modalities along with the pathways involved in the pathogenesis of this malignancies.