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Cancer Epidemiology, Biomarkers &... Dec 2022Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated...
BACKGROUND
Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups.
METHODS
The Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal immunochemical test (FIT, OC-Sensor; cutoffs: 10/20/47 μg Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of €20,000 per life-years gained (LYG).
RESULTS
Overall, the optimal surveillance strategy was annual FIT (47 μg) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:€18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 μg) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER:€15,000/LYG), and when treated with IRT and procarbazine, annual FIT (47 μg) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:€13,000/LYG).
CONCLUSIONS
Colorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy.
IMPACT
Colorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors.
Topics: Humans; Middle Aged; Aged; Adult; Cost-Benefit Analysis; Hodgkin Disease; Procarbazine; Early Detection of Cancer; Colorectal Neoplasms; Occult Blood; Colonoscopy; Survivors
PubMed: 36166472
DOI: 10.1158/1055-9965.EPI-22-0019 -
Journal of Cancer Research and... 2020Hodgkin's lymphoma (HL) can be treated with combined modality treatment (CMT) to limit long-term toxicities in the early favorable stage. Early unfavorable and advanced...
BACKGROUND
Hodgkin's lymphoma (HL) can be treated with combined modality treatment (CMT) to limit long-term toxicities in the early favorable stage. Early unfavorable and advanced stage HL is mainly treated with chemotherapy followed by radiation to the bulky site. This study examines the impact of CMT in early as well as advanced stage HL.
MATERIALS AND METHODS
From 2001 to 2011, 125 patients with Stage I to IV HL were analyzed. Median age of the patients was 25 years (range 12-68 years). CMT, chemotherapy, and radiation alone were given to 51, 64, and 10 patients, respectively. Chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was given to 100 patients, 6 patients received ABVD-like regimen, and 9 patients received cyclophosphamide, vincristine, procarbazine, and prednisone regimen. Radiotherapy (RT) was given to 61 (49%) patients, involved field RT to 55 (90%), and extended-field RT to 6 (10%) patients, respectively. Median radiation dose was 30 Gy (18-40 Gy).
RESULTS
All 25 patients with early-stage achieved complete response (CR) with CMT. At a median follow-up of 70 months (range 12-230 months), relapse was seen in two patients (1 local and 1 distant). Of 26 patients with advanced stage, 25 achieved a CR and 1 had stable disease with CMT. Relapse occurred in one patient (distant). In patients with early-stage treated with chemotherapy only ( n = 30, 24%), 9 patients had relapse (4 local and 5 distant) while in those with RT only ( n = 10, 8%), 4 developed distant relapse. In patients with advanced stage treated with chemotherapy only ( n = 34, 27%), 8 relapsed (5 local and distant, 3 distant only). Patients with relapse were salvaged with CMT ( n = 6), chemotherapy ( n = 15), or RT ( n = 3). Two patients have died. Five years' disease-free survival (DFS) in patients with early favorable stage, early unfavorable stage, and advanced stage was 91%, 82%, and 73%, respectively ( P = 0.026). DFS was significantly better with CMT than chemotherapy or radiation alone. Five years' overall survival (OS) was 93%, 92%, and 84%, respectively ( P = 0.139). Second malignancy occurred in 3 (2.4%) patients; carcinoma of the tongue, pseudomyxoma peritonei, and non-HL each, respectively. None of these patients had received prior radiation.
CONCLUSION
CMT improved DFS in patients with HL. OS was similar in all patients irrespective of treatment combinations. The incidence of second malignancy was 2.4%.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prednisone; Procarbazine; Radiotherapy; Survival Rate; Treatment Outcome; Vinblastine; Vincristine; Young Adult
PubMed: 32362601
DOI: 10.4103/jcrt.JCRT_465_17 -
Scientific Reports Jan 2021With the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma... (Meta-Analysis)
Meta-Analysis Review
With the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.
Topics: Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Clinical Trials as Topic; Disease-Free Survival; Dose-Response Relationship, Drug; Humans; Lymphoma, Non-Hodgkin; Methotrexate; Remission Induction; Treatment Outcome
PubMed: 33483528
DOI: 10.1038/s41598-020-80724-0 -
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 B.U.ON. : Official Journal... 2021To assess the efficacy and tolerance of proton re-irradiation in patients with unresectable recurrence of previously irradiated brain gliomas.
PURPOSE
To assess the efficacy and tolerance of proton re-irradiation in patients with unresectable recurrence of previously irradiated brain gliomas.
METHODS
Between February 2016 and December 2019, 44 patients with in-field recurrence after prior irradiation of brain gliomas were irradiated with intensity-modulated proton therapy. Seven patients (15.9%) originally had low-grade (WHO grade I-II) gliomas, nine patients (20.4%) had anaplastic astrocytoma (WHO grade III), and 28 patients (63.7%) had glioblastoma (WHO grade IV). All tumors were unresectable due to their localization. After a median time from the prior irradiation of 28.0 months [range, 12 to 173], patients received PT with 2.0 and 3.0 GyRBE per fraction, with median proton EQD2 (/=10) to a tumor of 55.0 GyRBE [range, 46.0 to 61.75]. Adjuvant chemotherapy (Temozolomide, or Procarbazine, Lomustine and vincristine, or Bevacizumab with Irinotecan) received 86.9% of the patients (n=40). Treatment-related toxicity was reported following CTCAE.
RESULTS
The median survival time was 12 months, with 1-year and 2-years overall survival (OS) amounting to 49.6% and 35.1%, respectively. The median progression-free survival (PFS) was 9 months, with 1- and 2-years PFS of 30.5% and 10.2%, respectively. Twenty-six patients died by the time of analysis; among them were 5 non-cancer deaths (19.2%), and 4 patients (15.4%) died of chemotherapy-associated severe toxicity. The incidence rate of radiation-induced necrosis was 6.8% (3 events).
CONCLUSIONS
Based on our results, we suggest re-irradiation of recurrent brain gliomas with proton therapy is able to achieve reasonable tumor control. Low adverse events rate and promising outcomes make it a safe treatment option with curative intent, even in unresectable cases.
Topics: Adult; Aged; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Progression-Free Survival; Proton Therapy; Re-Irradiation; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 34268961
DOI: No ID Found -
Biology Aug 2021Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently... (Review)
Review
Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly applied in the therapy of non-Hodgkin lymphoma and other malignancies, in which it is combined with drugs of different mechanisms of action, mainly with DNA-interacting compounds (for example cyclophosphamide), or drugs interfering with DNA synthesis (for example methotrexate). Besides, co-administration of vincristine with monoclonal antibodies has also emerged, the typical example of which is the anti-CD20 antibody rituximab. Although in some combination anticancer therapies, vincristine has been replaced with other drugs exhibiting lesser side effects, though, in most cases, it is still irreplaceable. This is strongly evidenced by the number of active clinical trials evaluating vincristine in combination cancer therapy. Therefore, in this article, we have reviewed the most common cancer treatment regimens employing vincristine and bring an overview of current trends in the clinical development of this compound.
PubMed: 34571726
DOI: 10.3390/biology10090849 -
Journal of Clinical Oncology : Official... Apr 2022The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results.
METHODS
Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2- and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment.
RESULTS
In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2-/PET4-, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4- and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4- patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; = .038) had a significant lower OS than PET2-/PET4- patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively.
CONCLUSION
The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Follow-Up Studies; Hodgkin Disease; Humans; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Positron-Emission Tomography; Prednisone; Procarbazine; Vinblastine; Vincristine; Young Adult
PubMed: 34990281
DOI: 10.1200/JCO.21.01777 -
Neuro-oncology Advances 2021Anaplastic pleomorphic xanthoastrocytoma (APXA) is a rare subtype of CNS astrocytoma. They are generally treated as high-grade gliomas; however, uncertainty exists...
BACKGROUND
Anaplastic pleomorphic xanthoastrocytoma (APXA) is a rare subtype of CNS astrocytoma. They are generally treated as high-grade gliomas; however, uncertainty exists regarding the optimal therapy. Here, we report on 3 pediatric cases of APXA.
METHODS
Our institutional database was queried for cases of APXA and 3 cases were identified. Surgical samples were processed for methylation profiling and chromosomal microarray analysis. Methylation data were uploaded to the online CNS tumor classifier to determine methylation-based diagnoses to determine copy number variations (CNVs).
RESULTS
Two patients were male, 1 female, and all were aged 12 years at diagnosis. All underwent a gross total resection (GTR) and were diagnosed with an APXA. Immunohistochemical analysis demonstrated that 2 cases were BRAF V600E positive. Methylation-based tumor classification supported the APXA diagnosis in all cases. CNV analyses revealed homozygous deletions in all and chromosome 9p loss in 2 cases. All patients received radiation therapy (54 Gy in 30 fractions) with concurrent temozolomide. Two patients received maintenance chemotherapy with temozolomide and lomustine for 6 cycles as per the Children's Oncology Group ACNS0423. The third patient recurred and went on to receive a second GTR and 6 cycles of lomustine, vincristine, and procarbazine. All are alive with no evidence of disease >4 years post-treatment completion (overall survival = 100%, event free survival = 67%).
CONCLUSIONS
The natural history and optimal treatment of this rare pediatric tumor are not well understood. This case series supports the use of adjuvant chemoradiotherapy in the treatment of APXA. The genetic landscape may be informative for optimizing treatment and prognosis.
PubMed: 33543147
DOI: 10.1093/noajnl/vdaa176 -
Oncology Letters Apr 2022Procarbazine, lomustine and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma; however, its significant toxicities frequently lead to dose...
Procarbazine, lomustine and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma; however, its significant toxicities frequently lead to dose reduction or discontinuation in patients with recurrent glioma. The current study evaluated the safety and efficacy of modified procarbazine and lomustine (PC) chemotherapy that omits vincristine and reduces the lomustine dose compared with those of conventional PCV chemotherapy. Using electronic medical records, all patients with adult recurrent glioma who received PC or PCV chemotherapy between 2009 and 2020 at Seoul St. Mary's Hospital or St. Vincent's Hospital were examined retrospectively. A total of 59 patients met the eligibility criteria. Among them, 15 patients received modified PC chemotherapy (PC group) and 44 patients received PCV chemotherapy (PCV group). The PC group presented a significantly lower hematology toxicity (anemia, 6.7 vs. 45.5%, P=0.02; thrombocytopenia 20.0 vs. 70.4%, P<0.001). Additionally, the clinical impacts of PC chemotherapy, including delay of a cycle, dose reduction, discontinuation of drug(s) or total cessation of chemotherapy, were significantly less frequent compared with the PCV group (26.7 vs. 68.2%, P=0.012). The overall survival of the PC group was also significantly longer than that of PCV group (396 vs. 232 days, P=0.042), while there was no significant difference in progression-free survival between the two groups (284.5 vs. 131 days, P=0.077). The results suggested that modified PC chemotherapy may be an alternative chemotherapeutic regimen with tolerable toxicity and without loss of clinical efficacy in patients with recurrent adult glioma. Further prospective and larger studies are required to validate our findings.
PubMed: 35251345
DOI: 10.3892/ol.2022.13234 -
Environmental and Molecular Mutagenesis Jul 2019Procarbazine hydrochloride (PCH) is a DNA-reactive hematopoietic carcinogen with potent and well-characterized clastogenic activity. However, there is a paucity of in...
Integrated In Vivo Genotoxicity Assessment of Procarbazine Hydrochloride Demonstrates Induction of Pig-a and LacZ Mutations, and Micronuclei, in MutaMouse Hematopoietic Cells.
Procarbazine hydrochloride (PCH) is a DNA-reactive hematopoietic carcinogen with potent and well-characterized clastogenic activity. However, there is a paucity of in vivo mutagenesis data for PCH, and in vitro assays often fail to detect the genotoxic effects of PCH due to the complexity of its metabolic activation. We comprehensively evaluated the in vivo genotoxicity of PCH on hematopoietic cells of male MutaMouse transgenic rodents using a study design that facilitated assessments of micronuclei and Pig-a mutation in circulating erythrocytes, and lacZ mutant frequencies in bone marrow. Mice were orally exposed to PCH (0, 6.25, 12.5, and 25 mg/kg/day) for 28 consecutive days. Blood samples collected 2 days after cessation of treatment exhibited significant dose-related induction of micronuclei in both immature and mature erythrocytes. Bone marrow and blood collected 3 and 70 days after cessation of treatment also showed significantly elevated mutant frequencies in both the lacZ and Pig-a assays even at the lowest dose tested. PCH-induced lacZ and Pig-a (immature and mature erythrocytes) mutant frequencies were highly correlated, with R values ≥0.956, with the exception of lacZ vs. Pig-a mutants in mature erythrocytes at the 70-day time point (R = 0.902). These results show that PCH is genotoxic in vivo and demonstrate that the complex metabolism and resulting genotoxicity of PCH is best evaluated in intact animal models. Our results further support the concept that multiple biomarkers of genotoxicity, especially hematopoietic cell genotoxicity, can be readily combined into one study provided that adequate attention is given to manifestation times. Environ. Mol. Mutagen. 60:505-512, 2019. © 2018 Her Majesty the Queen in Right of Canada.
Topics: Animals; Carcinogens; Cell Nucleus; DNA Damage; Erythrocytes; Hematopoietic Stem Cells; Lac Operon; Male; Mice; Micronucleus Tests; Mutagenesis; Mutagenicity Tests; Mutagens; Mutation; Procarbazine; Reticulocytes
PubMed: 30592561
DOI: 10.1002/em.22271