-
CNS Oncology 2015Anaplastic oligodendrogliomas (AOs) are rare brain tumors responsive to chemotherapy with procarbazine, lomustine (CCNU) and vincristine (PCV), especially when harboring... (Review)
Review
Anaplastic oligodendrogliomas (AOs) are rare brain tumors responsive to chemotherapy with procarbazine, lomustine (CCNU) and vincristine (PCV), especially when harboring 1p19q codeletion. However, with the emergence of temozolomide as an easier to administer and less toxic alternative regimen, PCV fell out of favor. Now, long-term results of two Phase III studies conceived in the 1990s, Radiation Therapy Oncology Group (RTOG) 9402 and European Organisation for Research and Treatment of Cancer (EORTC) 26951, resurrected debate about the potential role of PCV. No adequately powered prospective trial has compared chemotherapy alone with PCV versus temozolomide for newly diagnosed 1p19q codeleted AOs. Available data suggest responses may be both more frequent and more durable with PCV, and survival may be longer. Which regimen is 'better', therefore, depends on the importance of different metrics (i.e., toxicity, complexity, efficacy), and await definitive results from the important ongoing and recently redesigned CODEL international Phase III trial.
Topics: Antineoplastic Agents; Brain Neoplasms; Clinical Trials as Topic; Dacarbazine; Humans; Lomustine; Oligodendroglioma; Procarbazine; Temozolomide; Treatment Outcome; Vincristine
PubMed: 26544062
DOI: 10.2217/cns.15.36 -
Blood Apr 2018With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients.... (Review)
Review
With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Male; Neoplasm Staging; Positron-Emission Tomography; Prednisone; Procarbazine; Risk Assessment; Sex Factors; Survival Rate; Vinblastine; Vincristine
PubMed: 29500174
DOI: 10.1182/blood-2017-10-772665 -
Hematology. American Society of... Dec 2016Treating Hodgkin lymphoma by using chemotherapy with or without radiotherapy is highly successful, with substantially fewer deaths from lymphoma than from other causes... (Review)
Review
Treating Hodgkin lymphoma by using chemotherapy with or without radiotherapy is highly successful, with substantially fewer deaths from lymphoma than from other causes in recent studies of both early-stage and advanced-stage disease. Long-term toxicity is a major consideration in this context, and recent trials have used functional imaging with [F]fluorodeoxyglucose (FDG) positron emission tomography early in the course of treatment (interim PET) to assess response and modulate subsequent therapy. In early-stage disease, this has allowed omission of consolidation radiotherapy after a good response to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, and trials have shown that this can be done without detriment to overall survival, despite a small increase in rates of recurrence of ∼5%. Conversely, escalation to more intensive chemotherapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) for those with positive interim PET scans seems to be an effective strategy with improved disease control. In advanced-stage disease, several groups have elected to start treatment with ABVD and escalate to BEACOPP or myeloablative therapy for patients who remain PET positive after 2 cycles, which gives rates of disease control of ∼65%. De-escalation by omission of bleomycin and consolidation radiotherapy after a negative interim PET scan seems safe with no increase in recurrence rate, but the performance of interim PET after ABVD is suboptimal, especially for those with very advanced disease at presentation; recurrence rates after a negative scan are ∼15%. The negative predictive value of PET is higher after escalated BEACOPP chemotherapy, and the approach of initially treating with BEACOPP and de-escalating to ABVD for those with negative interim PET scans shows promising early results. Response-adapted therapy has yielded important results for patients with Hodgkin lymphoma and is becoming established as a standard approach.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemoradiotherapy; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Glucose-6-Phosphate; Hodgkin Disease; Humans; Positron-Emission Tomography; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 27913497
DOI: 10.1182/asheducation-2016.1.316 -
The Cochrane Database of Systematic... Jul 2017Recurrent high-grade glioma (HGG) carries an extremely poor prognosis. There is no current standard of care or guideline-based recommendations. Nitrosourea-based... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recurrent high-grade glioma (HGG) carries an extremely poor prognosis. There is no current standard of care or guideline-based recommendations. Nitrosourea-based multidrug chemotherapy or PCV - procarbazine, lomustine (CCNU) and vincristine - is one of the treatment options at recurrence. There has been no meta-analysis which looks at the benefits and harms of PCV chemotherapy in adults with recurrent HGG.
OBJECTIVES
To assess the effectiveness and safety of procarbazine, lomustine, and vincristine (PCV) chemotherapy with other interventions in adults with recurrent high-grade glioma. To investigate whether predefined subgroups of people benefit more or less from chemotherapy.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2017), MEDLINE (1946 to 22 May 2017), and Embase (1980 to 22 May 2017). We searched trial registries including the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch) and the National Institutes of Health (NIH; ClinicalTrials.gov). We searched the reference lists of all identified studies; the electronic table of contents of the Journal of Neuro-Oncology (1983 to 2016) and Neuro-Oncology (1999 to 2016); and conference abstracts from the Society for Neuro-Oncology (SNO) and the American Society of Clinical Oncology (ASCO 2004 to 2016). We also searched unpublished grey literature and other regional databases. There were no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs), quasi-randomised trials (QRCTs), or controlled clinical trials (CCTs) where PCV was used to treat adults with recurrent HGG. Comparison arm included no chemotherapy, other second line chemotherapy or best supportive care.
DATA COLLECTION AND ANALYSIS
Two review authors extracted the data and undertook a 'Risk of bias' assessment and critical appraisal of the studies.
MAIN RESULTS
We identified two RCTs meeting our inclusion criteria. The two trials tested different comparisons.One RCT included 35 participants and compared PCV with 'eight drugs in one day' multidrug chemotherapy, which is a combination of drugs with different mechanisms of action. Median survival was 6 months for the PCV group and 6.5 months for the 'eight drugs in one day' group. Adverse event outcomes were not graded or quantified. Progression-free survival (PFS) and quality of life (QoL) were not described in the methods and were not an outcome of interest. The sample size in this study was small, which lead to insufficient statistical power to detect clinical differences. According to the GRADE approach we judged the quality of evidence to be low for survival outcome and very low for chemotherapy toxicityThe second multi-institutional RCT included 447 participants and compared PCV with Temozolomide (TMZ). Participants were randomised into three arms to receive PCV, and two different regimens of TMZ in a 2:1:1 ratio at first recurrence. The trial reported a median overall survival of 6.7 months and 7.2 months for the PCV and TMZ group respectively. It reported a PFS of 3.6 months for the PCV group and 4.7 months for the TMZ group. There was no observed difference of effect on overall survival (hazard ratio (HR) 0.91, 95% CI 0.74 to 1.11; P = 0.35) or PFS (HR 0.89, 95% CI 0.73 to 1.08; P = 0.23) in participants receiving PCV or TMZ chemotherapy. The proportion of people with at least one grade 3 or 4 adverse event was not clinically important at 9.2% versus 12.2% in PCV and TMZ arms respectively. Mean QoL scores calculated at baseline, 12 weeks and 24 weeks was 51.9 versus 59.8 favouring TMZ (P = 0.04) which is statistically but not clinically significant and was less than the pre-defined 10 point change for moderate improvement. We judged the GRADE quality of evidence to be moderate for overall survival, PFS, and chemotherapy toxicity and low for QoL.
AUTHORS' CONCLUSIONS
Evidence is based on a single large trial analysis as the other trial was small, with inadequate power to detect survival difference. Chemotherapy-naive patients with HGG at first recurrence when treated with PCV or TMZ have similar survival and time-to-progression outcomes. Adverse events are similar and QoL scores are statistically but not clinically significant between TMZ and PCV. Further RCTs should be conducted with adequate power following CONSORT guidelines with emphasis on QoL outcomes.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cytarabine; Dacarbazine; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Glioma; Humans; Hydroxyurea; Lomustine; Methylprednisolone; Middle Aged; Neoplasm Recurrence, Local; Procarbazine; Randomized Controlled Trials as Topic; Temozolomide; Vincristine
PubMed: 28744879
DOI: 10.1002/14651858.CD011773.pub2 -
Turkish Journal of Haematology :... May 2019
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Eruptions; Etoposide; Female; Hodgkin Disease; Humans; Prednisone; Procarbazine; Vincristine
PubMed: 30600679
DOI: 10.4274/tjh.galenos.2019.2018.0317 -
Current Oncology (Toronto, Ont.) Feb 2018Procarbazine, lomustine, and vincristine (pcv) significantly improve survival outcomes in lgg (low-grade gliomas). Administration of pcv to lgg patients increased...
BACKGROUND
Procarbazine, lomustine, and vincristine (pcv) significantly improve survival outcomes in lgg (low-grade gliomas). Administration of pcv to lgg patients increased tremendously over the past years as it went from 2 patients per year between 2005 and 2012 to 23 patients in 2015 only in our centre. However, serious hematological and non-hematological adverse events may occur. The purpose of this study was to evaluate the toxicity of pcv and its clinical relevance in our practice.
METHODS
We retrospectively reviewed the charts of 57 patients with lgg who received pcv at the Centre hospitalier de l'Université de Montréal between 1 January 2005 and 27 July 2016.
RESULTS
Procarbazine, lomustine, and vincristine were associated with severe hematological toxicity as clinically significant grade 3 anemia, neutropenia, and thrombocytopenia occurred in 7%, 10%, and 28% of patients, respectively. Other frequent adverse events such as the increase of liver enzymes, cutaneous rash, neurotoxicity, and vomiting occurred in 65%, 26%, 60%, and 40% of patients, respectively. Patients with prophylactic trimethoprim/sulfamethoxazole had more grade 3 hematological toxicity with pcv, especially anemia ( = 0.040) and thrombocytopenia ( = 0.003) but we found no increase in pcv toxicity in patients on concurrent anticonvulsants. Patients with grade 3 neutropenia had a significantly lower survival (median survival 44.0 months vs. 114.0 months, = 0.001). Patients who were given pcv at diagnosis had more grade 3 anemia than those who received it at subsequent lines of treatment ( = 0.042).
CONCLUSION
Procarbazine, lomustine, and vincristine increase survival in lgg but were also associated with major hematologic, hepatic, neurologic, and cutaneous toxicity. Anti- pneumonia (pjp) prophylaxis, but not anticonvulsants, enhances hematologic toxicity.
PubMed: 29507493
DOI: 10.3747/co.25.3680 -
Proceedings of the Royal Society of... Jun 1974
Topics: Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Chemical Phenomena; Chemistry; DNA; DNA Replication; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Kinetics; Mechlorethamine; Prednisone; Procarbazine; Remission, Spontaneous; Structure-Activity Relationship; Vincristine
PubMed: 4851085
DOI: No ID Found -
Journal of Korean Medical Science Jun 2018While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the... (Clinical Trial)
Clinical Trial
BACKGROUND
While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O-methylguanine-DNA-methyltransferase (MGMT) promoter methylation.
METHODS
Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m) on day 1 and procarbazine (60 mg/m) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6).
RESULTS
One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities.
CONCLUSION
The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.
Topics: Adult; Aged; Antineoplastic Agents; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Dacarbazine; Disease-Free Survival; Female; Glioblastoma; Humans; Kaplan-Meier Estimate; Lomustine; Male; Middle Aged; Neoplasm Recurrence, Local; Procarbazine; Promoter Regions, Genetic; Temozolomide; Tumor Suppressor Proteins; Young Adult
PubMed: 29892208
DOI: 10.3346/jkms.2018.33.e167 -
JAMA Oncology Apr 2023Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy....
IMPORTANCE
Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear.
OBJECTIVE
To quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors.
DESIGN, SETTING, AND PARTICIPANTS
A nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022.
EXPOSURES
Mean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets.
MAIN OUTCOMES AND MEASURES
Excess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored.
RESULTS
The study population included 316 participants (mean [SD] age at HL diagnosis, 33.0 [9.8] years; 221 [69.9%] men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio [RR], 2.4; 95% CI, 1.4-4.1) and those who received more than 8.4 g/m2 procarbazine (RR, 2.5; 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose: the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-g/m2 increase in procarbazine dose.
CONCLUSIONS AND RELEVANCE
This nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.
Topics: Male; Humans; Child; Female; Hodgkin Disease; Procarbazine; Case-Control Studies; Survivors; Colorectal Neoplasms
PubMed: 36729438
DOI: 10.1001/jamaoncol.2022.7153 -
Medicine Sep 2020Systematic evaluation of the effectiveness and safety of combined procarbazine, lomustine, and vincristine for treating recurrent high-grade glioma.
A comparative study of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma: A protocol for systematic review and meta-analysis.
BACKGROUND
Systematic evaluation of the effectiveness and safety of combined procarbazine, lomustine, and vincristine for treating recurrent high-grade glioma.
METHODS
Electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, WanFang, and China National Knowledge Infrastructure (CNKI) were used to search for studies related to the utilization of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma. Literature screening, extraction of data, and evaluation of high standard studies were conducted by 2 independent researchers. The robustness and strength of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic methodology for recurrent high-grade glioma was assessed based on the odds ratio (OR), mean differences (MDs), and 95% confidence interval (CI). RevMan 5.3 software was used for carrying out the statistical analysis.
RESULTS
These results obtained in this study will be published in a peer-reviewed journal.
CONCLUSION
Evidently, the conclusion of this study will provide an assessment on whether combined procarbazine, lomustine, and vincristine provides an effective and safe form of treatment for recurrent high-grade glioma.
SYSTEMATIC REVIEW REGISTRATION NUMBER
INPLASY202080078.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Glioma; Humans; Lomustine; Meta-Analysis as Topic; Neoplasm Grading; Neoplasm Recurrence, Local; Procarbazine; Systematic Reviews as Topic; Vincristine; Young Adult
PubMed: 32957367
DOI: 10.1097/MD.0000000000022238