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Cureus Oct 2020Background The role of Procarbazine Lomustine and Vincristine (PCV) chemotherapy is already established in terms of improving survival in low-grade glioma (LGG). This...
Background The role of Procarbazine Lomustine and Vincristine (PCV) chemotherapy is already established in terms of improving survival in low-grade glioma (LGG). This improved survival has led to the increasing administration of PCV to LGG patients over the past years. However, like other chemotherapies, serious hematological and non-hematological toxicities may occur. The purpose of this study was to evaluate the toxicity profile of PCV and its clinical relevance in our practice. Materials and Methods We reviewed 63 patients of LGG retrospectively who received chemotherapy PCV between January 2015 and January 2018 at Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore. Results Significant hematological toxicity as grade 3 anemia, thrombocytopenia, and neutropenia occurred in 19%, 27%, and 46% respectively with PCV. Other toxicities such as neurotoxicity, vomiting and derangement of liver enzymes occurred in 3.2%, 19%, and 19% respectively. Patients who were on concurrent anticonvulsants had no increase in PCV toxicity. Survival was not impacted by hematological toxicities up to grade 3. Conclusion PCV chemotherapy is associated with major hematological, hepatic, and clinical toxicities (vomiting, constipation, and neuropathy). Hematological toxicities influenced the course of treatment in terms of delays and interruptions.
PubMed: 33224664
DOI: 10.7759/cureus.11070 -
Journal of Gynecology Obstetrics and... May 2021Progress in oncology has improved patient survival. However, cancer chemotherapy can be gonadotoxic and affect their fertility. Recourse to fertility preservation before...
BACKGROUND
Progress in oncology has improved patient survival. However, cancer chemotherapy can be gonadotoxic and affect their fertility. Recourse to fertility preservation before starting these treatments is therefore necessary in order to allow a better life quality after survival. The aim of this work was to study the impact of chemotherapy on ovarian reserve by AMH measurement.
METHODS
This is a descriptive and longitudinal study from 2015 to 2018 carried out at Aziza Othmana hospital ART center in Tunis on patient aged less than 41 years who were candidates for fertility preservation. Patients included had AMH measurement prior to cancer treatment. We called them back to follow up the AMH level after chemotherapy. The AMH assay was performed by electrochemilumiescence technique. At the end, only 66 patients met the inclusion criteria.
RESULTS
The most frequent pathologies were Hodgkin's lymphoma and breast cancer. The mean age of patients was 26.7 ± 6.8. The most used chemotherapy protocols were BEACOPP, ABVD or the combination of both in lymphoma and FEC + TXT for breast cancer treatment. A significant difference between AMH before and after chemotherapy was found for BEACOPP and FEC + TXT protocols (p < 10 3). The patient's age was correlated with the AMH decrease after chemotherapy (r = 0.577, p < 10 3).
CONCLUSION
Our results showed that the high risk gonadotoxicity protocols were BEACOPP for lymphoma treatment and FEC + TXT for breast cancer treatment. However, studies with a larger sample and more time extended monitoring are necessary for a better gonadotoxicity understanding of the cancer treatments available today.
Topics: Adolescent; Adult; Anti-Mullerian Hormone; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Breast Neoplasms; Cyclophosphamide; Dacarbazine; Docetaxel; Doxorubicin; Epirubicin; Etoposide; Female; Fertility Preservation; Fluorouracil; Hodgkin Disease; Humans; Longitudinal Studies; Luminescent Measurements; Ovarian Reserve; Prednisone; Procarbazine; Vinblastine; Vincristine; Young Adult
PubMed: 33307239
DOI: 10.1016/j.jogoh.2020.102035 -
Cancer Discovery Apr 2023We present the first comprehensive investigation of clonal hematopoiesis (CH) in 2,860 long-term survivors of pediatric cancer with a median follow-up time of 23.5...
UNLABELLED
We present the first comprehensive investigation of clonal hematopoiesis (CH) in 2,860 long-term survivors of pediatric cancer with a median follow-up time of 23.5 years. Deep sequencing over 39 CH-related genes reveals mutations in 15% of the survivors, significantly higher than the 8.5% in 324 community controls. CH in survivors is associated with exposures to alkylating agents, radiation, and bleomycin. Therapy-related CH shows significant enrichment in STAT3, characterized as a CH gene specific to survivors of Hodgkin lymphoma, and TP53. Single-cell profiling of peripheral blood samples revealed STAT3 mutations predominantly present in T cells and contributed by SBS25, a mutational signature associated with procarbazine exposure. Serial sample tracking reveals that larger clone size is a predictor for future expansion of age-related CH clones, whereas therapy-related CH remains stable decades after treatment. These data depict the distinct dynamics of these CH subtypes and support the need for longitudinal monitoring to determine the potential contribution to late effects.
SIGNIFICANCE
This first comprehensive CH analysis in long-term survivors of pediatric cancer presents the elevated prevalence and therapy exposures/diagnostic spectrum associated with CH. Due to the contrasting dynamics of clonal expansion for age-related versus therapy-related CH, longitudinal monitoring is recommended to ascertain the long-term effects of therapy-induced CH in pediatric cancer survivors. See related commentary by Collord and Behjati, p. 811. This article is highlighted in the In This Issue feature, p. 799.
Topics: Humans; Child; Clonal Hematopoiesis; Hematopoiesis; Mutation; Hodgkin Disease; Survivors
PubMed: 36751942
DOI: 10.1158/2159-8290.CD-22-0956 -
Current Oncology Reports Jan 2021IDH-mutant low-grade gliomas (LGG) have emerged as a distinct clinical and molecular entity with unique treatment considerations. Here, we review updates in IDH-mutant... (Review)
Review
PURPOSE OF REVIEW
IDH-mutant low-grade gliomas (LGG) have emerged as a distinct clinical and molecular entity with unique treatment considerations. Here, we review updates in IDH-mutant LGG diagnosis and classification, imaging biomarkers, therapies, and neurocognitive and patient-reported outcomes.
RECENT FINDINGS
CDKN2A/B homozygous deletion in IDH-mutant astrocytoma is associated with shorter survival, similar to WHO grade 4. The T2-FLAIR mismatch, a highly specific but insensitive sign, is diagnostic of IDH-mutant astrocytoma. Maximal safe resection is currently indicated in all LGG cases. Radiotherapy with subsequent PCV (procarbazine, lomustine, vincristine) provides longer overall survival compared to radiotherapy alone. Temozolomide in place of PCV is reasonable, but high-level evidence is still lacking. LGG adjuvant treatment has important quality of life and neurocognitive side effects that should be considered. Although incurable, IDH-mutant LGG have a favorable survival compared to IDH-WT glioma. Recent advances in molecular-based classification, imaging, and targeted therapies will hopefully improve survival and quality of life.
Topics: Brain Neoplasms; Chromosomes, Human, Pair 1; DNA Mutational Analysis; Glioma; Humans; Isocitrate Dehydrogenase; Neoplasm Grading
PubMed: 33492489
DOI: 10.1007/s11912-020-01006-6 -
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 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 -
American Journal of Hematology Jun 2023There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We...
There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60-88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale-Geriatrics (CIRS-G) score was 6 (range, 0-27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high-dose methotrexate (HD-MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R-MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58-month median follow-up, median progression-free survival (PFS) and overall survival (OS) were 17 months (95% CI 13-22 months) and 43 months (95% CI 31-56 months), respectively. Three-year PFS and OS were highest with MTR (55% and 74%, respectively). With single-agent methotrexate ± rituximab, 3-year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS-G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3-year PFS was 65% versus 45% without maintenance (p = 0.02), with 3-year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD-MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.
Topics: Humans; Aged; Middle Aged; Aged, 80 and over; Rituximab; Methotrexate; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Activities of Daily Living; Retrospective Studies; Temozolomide; Lymphoma; Central Nervous System; Central Nervous System Neoplasms
PubMed: 36965007
DOI: 10.1002/ajh.26919 -
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 -
Expert Review of Hematology Aug 2020To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and A+AVD (brentuximab vedotin, with doxorubicin, vinblastine, and dacarbazine) for advanced-stage Hodgkin lymphoma (HL).
METHODS
A systematic literature review (SLR) was conducted on 29 July 2016 (updated 26 July 2018) to identify randomized controlled trials (RCTs) and non-RCTs assessing the treatment of newly-diagnosed advanced-stage HL with ABVD and BEACOPP (and their variants), and A+AVD.
RESULTS
The SLR identified 62 RCTs and 42 non-RCTs. Five-year overall survival rates for ABVD and BEACOPP were 60-97% and 84-99%, and 5-year progression-free survival rates were 58-81% and 83-96%, respectively. Both regimens were associated with tolerability issues and side effects. Discontinuation or dose reduction of bleomycin resulted in fewer adverse events, without significantly affecting efficacy. A head-to-head trial demonstrated improved efficacy for A+AVD vs ABVD, with an acceptable tolerability profile. No data from head-to-head trials comparing A+AVD with BEACOPP were available, and an indirect treatment comparison was not feasible.
CONCLUSION
New therapies, such as A+AVD, maintain the efficacy observed with current treatments, and may provide a more tolerable treatment option for patients with advanced-stage HL.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Diagnostic Imaging; Disease Management; Hodgkin Disease; Humans; Neoplasm Staging; Prognosis; Publication Bias; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32749937
DOI: 10.1080/17474086.2020.1793666 -
Journal of Clinical Oncology : Official... Jul 2023Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the...
PURPOSE
Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.
METHODS
Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.
RESULTS
The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer.
CONCLUSION
To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.
Topics: Child; Humans; Adolescent; Cancer Survivors; Follow-Up Studies; Ifosfamide; Case-Control Studies; Procarbazine; Risk Factors; Bone Neoplasms; Cyclophosphamide; Osteosarcoma; Alkylating Agents; Neoplasms, Second Primary; Dose-Response Relationship, Radiation
PubMed: 37235821
DOI: 10.1200/JCO.22.02045