-
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 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Yonsei Medical Journal Jan 2024Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity...
PURPOSE
Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN).
MATERIALS AND METHODS
A total of 67 patients treated between 2009 and 2019 were analyzed. SRN was defined according to the following three criteria: 1) radiographic findings, 2) symptoms attributable to the lesion, and 3) treatment resulting in symptom improvement. Various contours, including the fornix, were delineated. Univariate and multivariate analyses of the relationship between RT dose and SRN, as well as receiver operating characteristic curve analysis for cut-off values, were performed.
RESULTS
The most common location was the frontal lobe (n=40, 60%). Gross total resection was performed in 38 patients (57%), and 42 patients (63%) received procarbazine, lomustine, and vincristine chemotherapy. With a median follow-up of 42 months, the median overall and progression-free survival was 74 months. Sixteen patients (24%) developed SRN. In multivariate analysis, age and maximum dose to the fornix were associated with the development of SRN. The cut-off values for the maximum dose to the fornix and age were 59 Gy (equivalent dose delivered in 2 Gy fractions) and 46 years, respectively. The rate of SRN was higher in patients whose maximum dose to the fornix was >59 Gy (13% vs. 43%, =0.005).
CONCLUSION
The maximum dose to the fornix was a significant factor for SRN development. While fornix sparing may help maintain neurocognitive function, additional studies are needed.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Vincristine; Radiation Dosage; Necrosis
PubMed: 38154474
DOI: 10.3349/ymj.2023.0112 -
Veterinary and Comparative Oncology Mar 2024The most commonly utilized protocols to treat lymphoma in cats employ vincristine, cyclophosphamide and prednisone; with additional drugs sometimes used including...
Treatment of feline intermediate to high-grade alimentary lymphoma: A retrospective evaluation of 55 cats treated with the VAPC combination chemotherapy protocol (2017-2021).
The most commonly utilized protocols to treat lymphoma in cats employ vincristine, cyclophosphamide and prednisone; with additional drugs sometimes used including L-asparaginase and doxorubicin. Medical records were reviewed for 55 cats with alimentary lymphoma treated with a novel multiagent protocol using prednisolone, L-asparaginase, doxorubicin, vinblastine instead of vincristine, a higher dosage of cyclophosphamide and oral procarbazine (VAPC protocol). Outcomes evaluated were response to therapy, toxicity and progression-free survival (PFS). Grade 3 or 4 neutropenia was the most common treatment-related reason for chemotherapy dosage adjustment, occurring in 8 of 52 cats receiving vinblastine, 7 of 55 cats receiving cyclophosphamide and 1 of 40 cats receiving doxorubicin, but febrile neutropenia was identified in only two cats. Of 38 cats receiving chemotherapy for measurable disease, 26 (68.4%) achieved complete response (CR). Three cats achieved a partial response and 9 cats failed to achieve a remission. There were no identified factors influencing whether a cat was likely to achieve CR. For all 55 cats (including those receiving chemotherapy and surgery), median PFS was 184 days with 1, 2 and 3-year survival rates of 35.4%, 26.5% and 26.5%, respectively. On multivariate analysis, 40 cats that achieved CR had a median survival time of 341 days (78 days for PR, 45 days for NR); PFS times were also significantly affected by lymphocyte:monocyte L:M ratio (>3.4 = 700 days vs. ≤3.4 = 126 days) and B-cell versus T-cell phenotype (220 days vs. 42 days, respectively).
Topics: Cats; Animals; Vincristine; Asparaginase; Retrospective Studies; Vinblastine; Lymphoma, Non-Hodgkin; Lymphoma; Prednisone; Cyclophosphamide; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Cat Diseases
PubMed: 38152842
DOI: 10.1111/vco.12958 -
Asian Journal of Neurosurgery Sep 2023The 2021 WHO Classification of Central Nervous System Tumors taxonomy laid further stress on molecular classification and prognostication of glial tumors in...
The 2021 WHO Classification of Central Nervous System Tumors taxonomy laid further stress on molecular classification and prognostication of glial tumors in comparison to histopathological grading. Research shows that low-grade gliomas (LGGs) can go through malignant differentiation and lead to severe disability and death. Data from various populations will be necessary to ascertain the exact interplay between genotypic predictors of LGG and outcomes. To assess the molecular pathology for glial tumors in the Pakistani population, the Shaukat Khanum Memorial Cancer Hospital carried out a retrospective chart review of electronic health records from 2008 to 2018, with immunohistochemistry analysis findings from 2010 to 2018. Patients with a pathological diagnosis of a glioma were included. Analysis was performed using IBM SPSS Statistics Version 23 and STATA Version 16. A -value of less than 0.05 was considered statistically significant with 95% confidence intervals reported. In all, 281 operable tumors were recorded. The most common procedure was a subtotal resection, and astrocytomas (64.77%) were the most common tumors. Radiation therapy and PCV (procarbazine, CCNU, and vincristine) was received by 85 patients, while radiation therapy and temozolomide were administered to 15 patients. Isocitrate dehydrogenase (IDH) wild-type LGG had a lower survival time, while improved survival times were seen for alpha-thalassemia X-linked intellectual disability syndrome (ATRX) retained and 1p19q co-deleted LGGs. Further studies are required to gain a better understanding of lower-grade glial tumor treatment and survival in Pakistan.
PubMed: 38152532
DOI: 10.1055/s-0043-1771369 -
Journal of Clinical Medicine Nov 2023The genotoxic methylating agents temozolomide (TMZ) and procarbazine and the chloroethylating nitrosourea lomustine (CCNU) are part of the standard repertoire in the... (Review)
Review
The genotoxic methylating agents temozolomide (TMZ) and procarbazine and the chloroethylating nitrosourea lomustine (CCNU) are part of the standard repertoire in the therapy of malignant gliomas (CNS WHO grade 3 and 4). This review describes the mechanisms of their cytotoxicity and cytostatic activity through apoptosis, necroptosis, drug-induced senescence, and autophagy, interaction of critical damage with radiation-induced lesions, mechanisms of glioblastoma resistance to alkylating agents, including the alkyltransferase MGMT, mismatch repair, DNA double-strand break repair and DNA damage responses, as well as IDH-1 and PARP-1. Cyclin-dependent kinase inhibitors such as regorafenib, synthetic lethality using PARP inhibitors, and alternative therapies including tumor-treating fields (TTF) and CUSP9v3 are discussed in the context of alkylating drug therapy and overcoming glioblastoma chemoresistance. Recent studies have revealed that senescence is the main trait induced by TMZ in glioblastoma cells, exhibiting hereupon the senescence-associated secretory phenotype (SASP). Strategies to eradicate therapy-induced senescence by means of senolytics as well as attenuating SASP by senomorphics are receiving increasing attention, with therapeutic implications to be discussed.
PubMed: 38068493
DOI: 10.3390/jcm12237442 -
Clinical Nuclear Medicine Jan 2024We aimed to assess the prognostic value of baseline tumor burden and dissemination parameters extracted from 18 F-FDG PET/CT in patients with early or advanced Hodgkin...
PURPOSE
We aimed to assess the prognostic value of baseline tumor burden and dissemination parameters extracted from 18 F-FDG PET/CT in patients with early or advanced Hodgkin lymphoma (HL) treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated BEACOPP (increased bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone).
PATIENTS AND METHODS
Patients aged ≥18 years with classical Hodgkin lymphoma were retrospectively included. Progression-free survival (PFS) analysis of dichotomized clinicobiological and PET/CT parameters (SUV max , TMTV, TLG, D max , and D bulk ) was performed. Optimal cutoff values for quantitative metrics were defined as the values maximizing the Youden index from receiver operating characteristic analysis. PFS rates were estimated with Kaplan-Meier curves, and the log-rank test was used to assess statistical significance. Hazard ratios were calculated using Cox proportional hazards models.
RESULTS
With a median age of 32 years, 166 patients were enrolled. A total of 111 patients had ABVD or ABVD-like treatment with or without radiotherapy and 55 patients with escalated BEACOPP treatment. The median follow-up was 55 months. Only International Prognostic Score (IPS >1), TMTV >107 cm 3 , and TLG >1628 were found to be significant prognostic factors for PFS on univariate analysis. Multivariate analysis revealed that IPS and TLG were independently prognostic and, combined, identified 4 risk groups ( P < 0.001): low (low TLG and low IPS; 4-year PFS, 95%), intermediate-low (high IPS and low TLG; 4-year PFS, 79%), intermediate-high (low IPS and high TLG; 4-year PFS, 78%), and high (high TLG and high IPS; 4-year PFS, 71%).
CONCLUSIONS
Combining baseline TLG with IPS could improve PFS prediction.
Topics: Adult; Humans; Adolescent; Hodgkin Disease; Prognosis; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Antineoplastic Combined Chemotherapy Protocols; Tumor Burden; Retrospective Studies; Doxorubicin; Bleomycin; Dacarbazine; Vinblastine
PubMed: 38015041
DOI: 10.1097/RLU.0000000000004930 -
International Journal of Hygiene and... Sep 2023Peripubertal concentrations of serum dioxins and polychlorinated biphenyls (PCBs) have demonstrated associations with altered age of pubertal onset and sexual maturity...
BACKGROUND
Peripubertal concentrations of serum dioxins and polychlorinated biphenyls (PCBs) have demonstrated associations with altered age of pubertal onset and sexual maturity in boys, but associations with pubertal progression have received less attention.
METHODS
The Russian Children's Study is a prospective cohort of 516 boys enrolled in 2003-2005 at age 8 or 9 and followed annually up to 19 years of age. Serum concentrations of dioxin-like toxic equivalents (TEQs), polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and non-dioxin-like PCBs (NDL-PCBs) and whole blood lead levels (BLLs) were quantified from blood samples collected at study entry (age 8-9). Testicular volume (TV) was assessed annually using a Prader orchidometer. Pubertal trajectories were identified by applying Group-Based Trajectory Models (GBTMs) to TV measured from ages 8-19. Associations of peripubertal serum TEQs, PCDDs, PCDFs, and NDL-PCBs with specific progression trajectories were modeled using multinomial logistic regression, adjusting for each boy's birthweight, and for BLL, body mass index and nutritional factors at study entry.
RESULTS
Among 489 eligible boys with available exposure measures, we identified three pubertal trajectories using GBTMs: slower (34% of boys), moderate (48%) and faster (18%). Boys with higher peripubertal serum TEQs had higher adjusted odds of being in the moderate versus faster trajectory (adjusted odds ratio (aOR) 1.79, 95% CI 1.01, 3.13) and the slower versus faster trajectory (aOR 1.52, 95% CI 0.82, 2.78) per 1 log unit increase in serum TEQs. Boys with higher peripubertal serum PCDFs had higher adjusted odds of being in the moderate compared to the faster trajectory (aOR 1.92, 95% CI 1.20, 3.03) and of being in the slower versus the faster trajectory (aOR 1.42, 95% CI 0.91, 2.33) per 1 log unit increase. Boys with higher NDL-PCBs had higher adjusted odds of being in the faster trajectory versus the moderate (aOR 2.56, 95% CI 0.91-7.20) or slower (aOR 3.31, 95% CI 1.07, 10.25) trajectory. Boys with higher blood lead levels also had higher adjusted odds of being in the slower trajectory of pubertal progression, compared to either the faster (aOR 1.47, 95% CI 0.89, 2.44) or moderate (aOR 1.20, 95% CI 0.83, 1.75) trajectories, per 1 log unit increase in BLL, although these associations did not attain statistical significance.
CONCLUSION
Boys' peripubertal exposure to dioxins and certain PCBs may alter pubertal progression.
Topics: Male; Child; Humans; Lead; Dioxins; Polychlorinated Biphenyls; Prospective Studies; Polychlorinated Dibenzodioxins; Dibenzofurans, Polychlorinated; Procarbazine; Russia
PubMed: 37981979
DOI: 10.1016/j.ijheh.2022.114096 -
Haematologica Nov 2023Hodgkin lymphoma (HL) treatment increases the risk of lung cancer. Most HL survivors are not eligible for lung cancer screening (LCS) programmes developed for the...
Hodgkin lymphoma (HL) treatment increases the risk of lung cancer. Most HL survivors are not eligible for lung cancer screening (LCS) programmes developed for the general population, and the utility of these programmes has not been tested in HL survivors. We ran a LCS pilot in HL survivors to describe screening uptake, participant characteristics, impact of a decision aid and screen findings. HL survivors treated ≥5 years ago with mustine/procarbazine and/or thoracic radiation, were identified from a follow-up database and invited to participate. Participants underwent a low-dose CT (LDCT) reported using protocols validated for the general population. Two hundred and eighteen individuals were invited, 123 were eligible, 102 were screened (58% response rate): 58% female, median age 52 years, median 22 years since HL treatment. 91.4% were deemed to have made an informed decision; participation was not influenced by age, gender, years since treatment or deprivation. Only 3/35 ever-smokers met criteria for LCS through the programme aimed at the general population. Baseline LDCT results were: 90 (88.2%) negative, 10 (9.8%) indeterminate, 2 (2.0%) positive. Two 3-month surveillance scans were positive. Of 4 positive scans, 2 patients were diagnosed with small-cell lung cancer; 1 underwent curative surgery. Coronary artery calcification was detected in 36.3%, and clinically significant incidental findings in 2.9%. LDCT protocols validated in ever-smokers can detect asymptomatic early-stage lung cancers in HL survivors. This finding, together with screening uptake and low false positive rates, supports further research to implement LCS for HL survivors.
PubMed: 37981893
DOI: 10.3324/haematol.2023.283287