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Journal of Veterinary Internal Medicine 2007Granulomatous meningoencephalomyelitis (GME) is an idiopathic inflammatory disease of the central nervous system. Remission often is short-lived in dogs treated with...
BACKGROUND
Granulomatous meningoencephalomyelitis (GME) is an idiopathic inflammatory disease of the central nervous system. Remission often is short-lived in dogs treated with glucocorticoids. Procarbazine is T cell-specific and crosses the blood-brain barrier.
HYPOTHESIS
Dogs with presumptive antemortem diagnosis of GME given procarbazine as adjunctive therapy to prednisone will have improved long-term outcome compared with dogs given no treatment or glucocorticoids alone.
ANIMALS
Two groups were studied: (1) Dogs with presumptive antemortem diagnosis of GME treated with procarbazine and prednisone (n = 21); (2) Dogs that had a histologic diagnosis of GME at postmortem examination and received no treatment (n = 11).
METHODS
Dogs with presumptive GME treated with procarbazine were identified retrospectively from medical records of 2 veterinary referral hospitals. Selection criteria required all dogs have a neurologic examination, blood work, cerebrospinal fluid analysis, and brain imaging (MRI or CT).
RESULTS
Median survival time for all dogs studied was 5.0 months. Median survival time for dogs treated with procarbazine was 14.0 months and for untreated dogs, 0.73 months. Treatment with procarbazine was significantly correlated with survival time (P < .001). Procarbazine was the only independent predictor of survival. Prednisone was reduced in dosage or discontinued in 17 dogs. Adverse reactions to procarbazine therapy included myelosuppression in 7 dogs and hemorrhagic gastroenteritis in 3 dogs.
CONCLUSION
These data suggest that procarbazine treatment of presumptive GME may result in greater improved long-term outcome than has been previously reported for glucocorticoid treatment alone and may complement other immunomodulatory therapies. Procarbazine-treated dogs must be monitored for adverse reactions.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Dog Diseases; Dogs; Drug Therapy, Combination; Meningoencephalitis; Prednisone; Procarbazine; Retrospective Studies
PubMed: 17338156
DOI: 10.1892/0891-6640(2007)21[100:paatft]2.0.co;2 -
Veterinary and Comparative Oncology Dec 2018Canine T cell lymphoma has previously been found to be a poor prognostic indicator compared with its B cell counterpart. The cyclophosphamide, doxorubicin, vincristine,...
Canine T cell lymphoma has previously been found to be a poor prognostic indicator compared with its B cell counterpart. The cyclophosphamide, doxorubicin, vincristine, and prednisolone protocol is widely accepted as a first line treatment for canine lymphoma. There have been several studies investigating alternative protocols for T cell lymphoma. This study investigated the use of a modified lomustine, vincristine, procarbazine and prednisolone protocol as a first line treatment in 35 dogs with T Cell lymphoma. Median progression free survival (PFS) time for all 35 dogs was 431 days with a 6-month, 1-year, 2-year, and 3-year PFS of 69%, 54%, 29%, and 12%. Median survival time (MST) was 507 days. Twenty-nine dogs attained a complete response and had a median PFS time of 509 days. Thirty dogs experienced adverse events during the protocol, with 73% of these being grade 1 or 2. This protocol has shown increased median PFS time and MST compared with previous studies and suggests its use as a first line chemotherapy protocol against canine T cell lymphoma.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Dog Diseases; Dogs; Female; Lomustine; Lymphoma, T-Cell; Male; Prednisolone; Procarbazine; Survival Analysis; Vincristine
PubMed: 30117253
DOI: 10.1111/vco.12430 -
Journal of Neurosurgery Oct 1996The authors provided procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy to 32 patients whose tumors contained varying mixtures of oligodendroglial and...
The authors provided procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy to 32 patients whose tumors contained varying mixtures of oligodendroglial and astrocytic cells. Twenty-five patients had oligodendroglioma-astrocytoma (oligoastrocytoma) with a histological Grade of III (19 patients) or IV (six patients); seven had anaplastic oligodendroglioma. The PCV therapy was administered every 6 weeks for a total of at least 124 cycles. The median duration of follow-up review from the start of chemotherapy was 19.3 months. Nineteen patients were treated before receiving radiation therapy and 12 after receiving it (one patient received concurrent radiotherapy and chemotherapy). Grade 3 or 4 hematological toxicity was experienced by nine (31%) of 29 patients. Ten patients had delayed treatment due to treatment-related toxicities (34.5%). Ninety-one percent of the 32 patients responded to the therapy. These included 10 patients with a complete response and 19 with a partial response. The median time to progression was 15.4 months for all patients and 23.2 months for those with Grade III tumors. The median time to progression for patients with Grade III oligoastrocytomas was 13.8 months; for those with Grade IV oligoastrocytoma it was 12.4 months and for those with anaplastic oligodendrogliomas it was 63.4 months (p = 0.0348). These patients survived a median of 49.8 months, 16 months, and 76 or more months, respectively, from the start of chemotherapy (p = 0.0154). The PCV therapy provides durable responses in patients with Grade III or IV oligoastrocytomas.
Topics: Adult; Astrocytoma; Brain Neoplasms; Female; Humans; Lomustine; Male; Middle Aged; Procarbazine; Prognosis; Time Factors; Vincristine
PubMed: 8814163
DOI: 10.3171/jns.1996.85.4.0602 -
Mutation Research Aug 2003Procarbazine [N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide], a hydrazine derivative, which has been shown to have effective antineoplastic activity, induces cancer...
Procarbazine [N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide], a hydrazine derivative, which has been shown to have effective antineoplastic activity, induces cancer in some experimental animals and humans. To clarify a new mechanism for its carcinogenic effect, we examined DNA damage induced by procarbazine in the presence of metal ion, using 32P-5'-end-labeled DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 protooncogene. Procarbazine plus Cu(II) induced piperidine-labile and formamidopyrimidine-DNA glycosylase-sensitive lesions at the 5'-ACG-3' sequence, complementary to a hotspot of the p53 gene, and the 5'-TG-3' sequence. Catalase partially inhibited DNA damage, suggesting that not only H(2)O(2) but also other reactive species are involved. Procarbazine plus Cu(II) significantly increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, which was completely inhibited by calatase. Electron spin resonance spin-trapping experiments revealed that methyl radicals were generated from procarbazine and Cu(II). On the basis of these findings, it is considered that procarbazine causes DNA damage through non-enzymatic formation of the Cu(I)-hydroperoxo complex and methyl radicals. In conclusion, in addition to alkylation, oxidative DNA damage may play important roles in not only antitumor effects but also mutagenesis and carcinogenesis induced by procarbazine.
Topics: Catalase; Copper; DNA Damage; Free Radicals; Genes, p53; Genes, ras; Humans; Oxidative Stress; Phenanthrolines; Procarbazine
PubMed: 12948823
DOI: 10.1016/s1383-5718(03)00157-8 -
Mutation Research Aug 1999Procarbazine, a drug used for cancer chemotherapy, is carcinogenic in rodent bioassays. We analyzed the mutagenicity of procarbazine in various organs and the...
Procarbazine, a drug used for cancer chemotherapy, is carcinogenic in rodent bioassays. We analyzed the mutagenicity of procarbazine in various organs and the clastogenicity of the drug in hematopoietic cells of the lacZ transgenic MutaMouse. This was part of the second collaborative study of the Mammalian Mutagenesis Study Group of the Japanese Environmental Mutagen Society on the transgenic mouse mutation assay. At 50 mg kg(-1), procarbazine induced micronuclei in hematopoietic cells, but it did not increase the lacZ mutant frequency (MF) in bone marrow. It was also negative in liver, testis, spleen, kidney, and lung. Five daily administrations of 150 mg kg(-1) yielded highly positive responses in the drug's target organs for carcinogenesis (lung, bone marrow, and spleen). Lower positive responses were detected in kidney, which is a minor target organ. Liver showed only a slight increase in lacZ MF and brain showed no increase. The testis MF more than doubled which suggest that procarbazine is mutagenic to germ cells. Thus, we demonstrated that procarbazine has a strong clastogenic effect in hematopoietic cells and is mutagenic in a variety organs after high dose treatment. The induced MF was especially high in procarbazine's target organs for carcinogenesis, which supports the relevance of the transgenic mouse mutation assay for the assessment of potential genotoxins in vivo.
Topics: Animals; Carcinogens; Lac Operon; Male; Mice; Mice, Transgenic; Micronucleus Tests; Mutagens; Mutation; Organ Specificity; Procarbazine; Time Factors
PubMed: 10521668
DOI: 10.1016/s1383-5718(99)00060-1 -
Environmental and Molecular Mutagenesis Oct 2020Procarbazine (PCZ) and N-propyl-N-nitrosourea (PNU) are rodent mutagens and carcinogens. Both induce GPI-anchored marker-deficient mutant-phenotype red blood cells...
Procarbazine (PCZ) and N-propyl-N-nitrosourea (PNU) are rodent mutagens and carcinogens. Both induce GPI-anchored marker-deficient mutant-phenotype red blood cells (RBCs) in the flow cytometry-based rat RBC Pig-a assay. In the present study, we traced the origin of the RBC mutant phenotype by analyzing Pig-a mutations in the precursors of RBCs, bone marrow erythroid cells (BMEs). Rats were exposed to a total of 450 mg/kg PCZ hydrochloride or 300 mg/kg PNU, and bone marrow was collected 2, 7, and 10 weeks later. Using a flow cell sorter, we isolated CD59-deficient mutant-phenotype BMEs from PCZ- and PNU-treated rats and examined their endogenous X-linked Pig-a gene by next generation sequencing. Pig-a mutations consistent with the properties of PCZ and PNU were found in sorted mutant-phenotype BMEs. PCZ induced mainly A > T transversions with the mutated A on the nontranscribed strand of the Pig-a gene, while PNU induced mainly T > A transversions with the mutated T on the nontranscribed strand. The treatment-induced mutations were distributed across the protein coding sequence of the Pig-a gene. The causal relationship between BMEs and RBCs and the agent-specific mutational spectra in CD59-deicient BMEs indicate that the rat RBC Pig-a assay, scoring CD59-deficient mutant-phenotype RBCs in peripheral blood, detects Pig-a gene mutation.
Topics: Animals; Antineoplastic Agents; Bone Marrow Cells; CD59 Antigens; Male; Membrane Proteins; Mutation; Nitrosourea Compounds; Procarbazine; Rats; Rats, Inbred F344; Rats, Sprague-Dawley
PubMed: 32729949
DOI: 10.1002/em.22402 -
Klinische Padiatrie Nov 2016Survival rates have been excellent in patients treated for Hodgkin lymphoma (HL) during childhood and adolescence. Unfortunately, severe treatment related late effects... (Review)
Review
Survival rates have been excellent in patients treated for Hodgkin lymphoma (HL) during childhood and adolescence. Unfortunately, severe treatment related late effects have been observed. It was therefore an important aim of the cooperative pediatric HL therapy studies in Germany to reduce the number of late effects without jeopardizing the excellent treatment results. Progress and relapses of HL were analyzed to obtain important information for the future salvage therapy. All late effects were documented and their etiologies analyzed. Information obtained from bacterial infections and late deaths following splenectomy were used to inform patients at risk and their local physicians about necessary preventive measurements. Procarbazine was recognized as major gonadotoxic agent in boys and eliminated successively from the treatment regimens. Parenthood was normal in female patients when compared to the German female population documenting normal ovarian function except in patients with pelvic radiation. Radiation was the most important risk factor for thyroid diseases, cardiac late effects and subsequent malignant neoplasms, especially thyroid and breast cancer. A special screening program was initiated for women with chest radiotherapy, since they had a high risk of breast cancer already at a young age. The results of the HL Late Effects Research Project are important for the aftercare of patients and for the design of future HL treatment regimens.
Topics: Adolescent; Child; Combined Modality Therapy; Early Detection of Cancer; Heart; Hodgkin Disease; Humans; Neoplasms, Radiation-Induced; Opportunistic Infections; Procarbazine; Radiation Injuries; Risk Factors; Salvage Therapy; Splenectomy; Survival Rate; Treatment Outcome
PubMed: 27846658
DOI: 10.1055/s-0042-110406 -
Journal of Feline Medicine and Surgery Apr 2020The aims of this study were to evaluate the safety of mustargen, vincristine, procarbazine and prednisone (MOPP) chemotherapy in the treatment of relapsed or refractory...
OBJECTIVES
The aims of this study were to evaluate the safety of mustargen, vincristine, procarbazine and prednisone (MOPP) chemotherapy in the treatment of relapsed or refractory feline lymphoma, and to determine the overall response rate and median remission time with this protocol.
METHODS
The medical records of 38 cats with relapsed or refractory lymphoma treated with MOPP chemotherapy at three institutions (University of Pennsylvania, the Animal Medical Center, and VCA Western Veterinary Specialist and Emergency Centre) were examined. Information evaluated included patient signalment, feline immunodeficiency virus/feline leukemia virus status, anatomic location(s) of lymphoma, prior protocols (type and number), MOPP doses, MOPP response, remission duration, hematologic and biochemical parameters, and owner-reported adverse effects.
RESULTS
Overall, 70.3% of cats responded to MOPP chemotherapy. Among the responders, the median remission duration was 166 days. The most common adverse effects were neutropenia and gastrointestinal upset, which were reported in 18.4% of cats. In 55.3% of cats, no adverse effects were reported. In total, 30.8% of responders continued to respond 6 months following the initiation of MOPP, and 15.4% maintained a response 1 year after starting MOPP.
CONCLUSIONS AND RELEVANCE
MOPP is a safe protocol for the treatment of relapsed or refractory feline lymphoma, with a promising overall response rate and median remission time.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cat Diseases; Cats; Lymphoma; Mechlorethamine; Prednisone; Procarbazine; Treatment Outcome; Vincristine
PubMed: 30994392
DOI: 10.1177/1098612X19841916 -
Journal of Oncology Pharmacy Practice :... Jul 2024Procarbazine is an oral chemotherapeutic agent used in the treatment of brain malignancies and is associated with hypersensitivity reactions. In case of grade 4...
INTRODUCTION
Procarbazine is an oral chemotherapeutic agent used in the treatment of brain malignancies and is associated with hypersensitivity reactions. In case of grade 4 reactions, rechallenge should be avoided, and the agent should be replaced, unless the treatment is curative, in which case the application of a desensitization protocol should be considered. We present a successful case of desensitization in procarbazine anaphylaxis.
CASE REPORT
A 53-year-old male patient was diagnosed with recurrent anaplastic oligodendroglioblastoma. The patient received three cycles of procarbazine, lomustine, and vincristine chemotherapy for malignancy recurrence. In the fourth cycle, on the 12th day of procarbazine treatment, the patient developed anaphylaxis. Procarbazine was given together with premedication as part of the 12-step desensitization process, and the fourth cycle was successfully completed.
MANAGEMENT AND OUTCOME
Procarbazine hypersensitivity reactions are observed less frequently than reactions to other chemotherapeutics. We presented a case of procarbazine-associated severe anaphylaxis that was able to continue procarbazine chemotherapy with successful desensitization. This case is important in terms of confirming the procarbazine desensitization protocol.
DISCUSSION
In literature there is only one protocol developed was successfully applied in one patient with procarbazine anaphylaxis. In the current case, we took this protocol into consideration in the management of our patient. Following the use of this protocol, the patient was able to continue procarbazine chemotherapy successfully. Procarbazine anaphylaxis is rare, and more cases are needed to be reported to confirm the desensitization protocol and when to continue procarbazine treatment.
Topics: Humans; Male; Middle Aged; Procarbazine; Anaphylaxis; Oligodendroglioma; Desensitization, Immunologic; Drug Hypersensitivity; Neoplasm Recurrence, Local; Brain Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38258352
DOI: 10.1177/10781552241226861 -
Carcinogenesis May 1992Electron spin resonance (ESR) analysis combined with the use of 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) and dibromonitroso benzenesulfonic acid (DBNBS) as...
Electron spin resonance (ESR) analysis combined with the use of 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) and dibromonitroso benzenesulfonic acid (DBNBS) as spin-trapping agents was used to characterize free radical generation during the metabolism of the anticancer agent procarbazine [N-isopropyl-a-(2-methylhydrazino)-p-toluamide hydrochloride]. The formation of free radical species, identified as methyl radicals, was observed during oxidation of procarbazine in rat liver microsomes and isolated hepatocytes in vitro, as well as in several organs following administration of the drug in vivo. A cytochrome P450-mediated reaction, involving P450IA and IIB isoenzymes, was responsible for the activation process. The metabolic pathway leading to free radical formation was characterized using various procarbazine metabolites and revealed strict analogies with previously published data on methane production from procarbazine. These results supported the identification of the trapped species as methyl free radical and suggested that C-oxidation of azoprocarbazine is the main source of radical intermediates derived from this anticancer drug.
Topics: Animals; Electron Spin Resonance Spectroscopy; Free Radicals; Hydrazones; Liver; Male; Microsomes, Liver; Monomethylhydrazine; NADP; Procarbazine; Rats
PubMed: 1316811
DOI: 10.1093/carcin/13.5.799