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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 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 -
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 -
Annals of Oncology : Official Journal... Jan 1991Initial results from studies with third-generation combination chemotherapy regimens for the treatment of aggressive non-Hodgkin's lymphomas (NHL) demonstrated complete... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial Review
Initial results from studies with third-generation combination chemotherapy regimens for the treatment of aggressive non-Hodgkin's lymphomas (NHL) demonstrated complete remission (CR) rates higher than those reported with first-generation regimens. Long-term follow-up of these studies is required to know if the increased number of CRs translates into an increased number of long-term disease-free survivors. In this report, results obtained with one of the third-generation regimens, ProMACE (prednisone/methotrexate/doxorubicin/cyclophosphamide/etoposide)-Cyta BOM (cytarabine/bleomycin/vincristine/methotrexate) are described. From 1981 to 1988, 193 patients with stage II, III, or IV aggressive NHL treated at the National Cancer Institute were randomly assigned to receive either ProMACE (day 1)-CytaBOM (day 8) or ProMACE (day 1)-MOPP (mechlorethamine/vincristine/procarbazine/prednisone) (day 8). With a median follow-up of 5 years, the CR rate was 86% for ProMACE-CytaBOM v 74% for ProMACE-MOPP (P = 0.048). A plateau in the disease-free survival curve is seen at 69% for ProMACE-CytaBOM v 54% for ProMACE-MOPP (P = 0.082). A plateau is also seen in the overall survival curves at 69% for ProMACE-CytaBOM v 53% for ProMACE-MOPP (P = 0.046). The Southwest Oncology Group also conducted a phase II study of ProMACE-CytaBOM in 78 patients with stages II to IV intermediate- or high-grade NHL to determine the CR rate and long-term disease-free survival of this regimen in a national cooperative group setting. The CR rate was 65%. With a median follow-up of 38 months, disease-free survival is 50% at 3 years and overall survival is 57% at the same time point.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Evaluation; Etoposide; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Mechlorethamine; Methotrexate; Middle Aged; Prednisone; Procarbazine; Remission Induction; Survival Rate; Vincristine
PubMed: 1710487
DOI: 10.1093/annonc/2.suppl_1.33 -
Neurologia Medico-chirurgica 2013World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the... (Comparative Study)
Comparative Study Review
World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the treatment outcome can still be improved. Review of previous clinical trials found the following: (1) GIIG increased in size by 3-5 mm per year when observed or treated with surgery alone; (2) after pathological diagnosis, the survival rate was increased by early aggressive tumor removal at an earlier stage compared to observation alone; (3) although the prognosis after total tumor removal was significantly better than that after partial tumor removal, half of the patients relapsed within 5 years; (4) comparing postoperative early radiotherapy (RT) and non-early RT after relapse, early RT prolonged progression-free survival (PFS) but did not affect overall survival (OS); (5) local RT of 45 to 64.8 Gy did not impact PFS or OS; (6) in patients with residual tumors, RT combined with chemotherapy (procarbazine plus lomustine plus vincristine) prolonged PFS compared with RT alone but did not affect OS; and (7) poor prognostic factors included astrocytoma, non-total tumor removal, age ≥40 years, largest tumor diameter ≥4-6 cm, tumor crossing the midline, and neurological deficit. To improve treatment outcomes, surgery with functional brain mapping or intraoperative magnetic resonance imaging or chemoradiotherapy with temozolomide is important. In this review, current knowledge regarding GIIG is described and treatment strategies are explored.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Cranial Irradiation; Craniotomy; Early Medical Intervention; Glioma; Humans; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Oligodendroglioma; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 23883553
DOI: 10.2176/nmc.53.429 -
Neuro-oncology Sep 2012Seizures represent a common symptom in low-grade gliomas; when uncontrolled, they significantly contribute to patient morbidity and negatively impact quality of life.... (Review)
Review
Seizures represent a common symptom in low-grade gliomas; when uncontrolled, they significantly contribute to patient morbidity and negatively impact quality of life. Tumor location and histology influence the risk for epilepsy. The pathogenesis of tumor-related epilepsy is multifactorial and may differ among tumor histologies (glioneuronal tumors vs diffuse grade II gliomas). Gross total resection is the strongest predictor of seizure freedom in addition to clinical factors, such as preoperative seizure duration, type, and control with antiepileptic drugs (AEDs). Epilepsy surgery may improve seizure control. Radiotherapy and chemotherapy with alkylating agents (procarbazine + CCNU+ vincristine, temozolomide) are effective in reducing the frequency of seizures in patients with pharmacoresistant epilepsy. Newer AEDs (levetiracetam, topiramate, lacosamide) seem to be better tolerated than the old AEDs (phenobarbital, phenytoin, carbamazepine), but there is lack of evidence regarding their superiority in terms of efficacy.
Topics: Anticonvulsants; Brain Neoplasms; Glioma; Humans; Neoplasm Grading; Seizures; Treatment Outcome
PubMed: 23095831
DOI: 10.1093/neuonc/nos199 -
The Oncologist May 2021IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine...
Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort.
BACKGROUND
IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear.
METHODS
In a large cohort of patients with histologically proven 2016 World Health Organization classification AA with IDH1/2 mutations included in the French national POLA cohort (n = 355), the primary objective was to compare progression-free survival (PFS) between the two treatment regimens (n = 311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity.
RESULTS
The 4-year PFS in the RT + PCV arm was 70.8% versus 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 (95% confidence interval [CI], 0.38-0.87; p = .0074) in univariable analysis and 0.63 (95% CI, 0.41-0.97; p = .0348) in multivariable analysis. The 4-year OS in the RT + PCV arm was 84.3% versus 76.6% in the RT + TMZ arm, with an HR of 0.57 (95% CI, 0.30-1.05; p = .0675) in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% vs. 8.6%, p < .0001).
CONCLUSION
RT + PCV significantly improved PFS compared with RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated.
IMPLICATIONS FOR PRACTICE
In the absence of fully conducted randomized trials comparing procarbazine, lomustine, and vincristine (PCV) with temozolomide (TMZ) in adjuvant treatment after radiotherapy (RT) for the management of IDH-mutant anaplastic astrocytoma (AA) and a similar level of evidence, these two chemotherapies are both equally recommended in international guidelines. This study in a national cohort of IDH-mutant AA defined according the 2016 World Health Organization (WHO) classification shows for the first time that the RT + PCV regimen significantly improves progression-free survival in comparison with the RT + TMZ regimen. Even if at the time of analysis the difference in overall survival was not significant, this result provides new evidence for the debate about the chemotherapy regimen to prescribe in adjuvant treatment to RT for WHO 2016 IDH-mutant AA.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Humans; Lomustine; Procarbazine; Retrospective Studies; Temozolomide; Vincristine
PubMed: 33524191
DOI: 10.1002/onco.13701 -
Anticancer Research 2005The safety, tolerance and preliminary efficacy of a chemotherapy regimen consisting of procarbazine (PCB), ranimustine (MCNU) and vincristine (VCR) were assessed for... (Clinical Trial)
Clinical Trial
UNLABELLED
The safety, tolerance and preliminary efficacy of a chemotherapy regimen consisting of procarbazine (PCB), ranimustine (MCNU) and vincristine (VCR) were assessed for patients with newly diagnosed supratentorial anaplastic oligodendroglioma.
MATERIALS AND METHODS
Between October 1999 and September 2003, 5 patients were enrolled. The initial regimens were prescribed as adjuvant therapy in conjunction with radiotherapy following standard surgical treatment. All patients received a chemotherapy comprising ranimustine (100 mg/m2) intravenously on Day 1, procarbazine (60 mg/m2) on Days 8 to 21, and vincristine (1.4 mg/m2, maximum total 2 mg) on Days 8 and 29. The cycles were repeated every 8 weeks until tumor progression was evident, or for a total of 6 cycles over a 1-year period. The primary end-points were safety and tolerability, while the secondary end-point was overall survival.
RESULTS
Five consecutive eligible patients were treated. Of the 4 evaluable patients, 3 partially responded to the treatment (PR), while 1 had a complete response (CR): all patients are still alive. However, 3 of the 5 patients showed relapse, with a time to tumor progression (TTP) of 50, 143 and 241 weeks, respectively. Two of these patients received combined treatment with carboplatin, etoposide and recombinant human mutant tumor necrosis factor-alpha at the first relapse. This regimen appeared to be safe and neither neurological toxicity, severe or life-threatening hematological toxicity, nor fatal toxicity (WHO Grade 4) were experienced.
CONCLUSION
These results suggest that a chemotherapy regimen consisting of PCB, MCNU and VCR in this patient population seems to be safe and tolerable, and the response rate was high. Thus, wide resection with a risk of major neurological morbidity due to nearby functionally critical areas can be avoided. However, since the relapse rate was high, a second-line chemotherapy should be developed for anaplastic oligodendroglioma to improve the long-term control of the disease.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Nitrosourea Compounds; Oligodendroglioma; Procarbazine; Treatment Outcome; Vincristine
PubMed: 16302731
DOI: No ID Found -
Oncology (Williston Park, N.Y.) Feb 1996In most patients with newly diagnosed Hodgkin's disease, initial therapy is curative. However, a small portion of patients treated with radiotherapy alone for limited... (Review)
Review
In most patients with newly diagnosed Hodgkin's disease, initial therapy is curative. However, a small portion of patients treated with radiotherapy alone for limited favorable disease, and a larger percentage of patients treated with combination chemotherapy, with or without radiotherapy, for advanced-stage or unfavorable disease relapse after initial remission. Patients relapsing after radiotherapy alone should do as well with salvage combination chemotherapy as patients with advanced disease who have never received radiation. In patients who relapse after combination chemotherapy, retreatment with the same regimen or employment of a non-cross-resistant regimen offers high response rates among those with favorable characteristics. However, long-term disease-free survival is achieved in a minority of these patients, and in even fewer of those with early relapse or other unfavorable characteristics. High-dose therapy with autografting shows the greatest promise in the treatment of patients at relapse.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Combined Modality Therapy; Dacarbazine; Doxorubicin; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Mechlorethamine; Prednisone; Procarbazine; Prognosis; Recurrence; Salvage Therapy; Time Factors; Transplantation, Autologous; Vinblastine; Vincristine
PubMed: 8838268
DOI: No ID Found -
BMC Cancer Feb 2021Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV...
BACKGROUND
Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV is associated with significant toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after 6 months. As patients on clinical trials may be fitter, we aimed to further explore the tolerability of PCV chemotherapy in routine clinical practice.
METHODS
We conducted a retrospective study between 2014 and 2018 at a National Neuro-Oncology centre. Patients who had received PCV during this time period were included. The primary objective was to assess tolerability of treatment. Secondary objectives included evaluation of treatment delays, dose modifications and toxicities.
RESULTS
Overall, 41 patients were included, 24 (58%) were male and 21 (51%) aged ≥40 years. 38 (93%) underwent surgical resection and all patients received adjuvant radiotherapy prior to chemotherapy. The median number of cycles completed was 3,2,4 for procarbazine, lomustine and vincristine respectively. Only 4 (10%) completed all 6 cycles of PCV without dose modifications. There was a universal decline in dose intensity as cycles of chemotherapy progressed. Dose intensity for cycle 1 versus cycle 6 respectively: procarbazine (98% versus 46%), lomustine (94% versus 48%) and vincristine (93% versus 50%). Haematological toxicities were common. Six (14%) patients experienced Grade III-IV thrombocytopaenia and 13 (31%) experienced Grade III-IV neutropaenia.
CONCLUSION
Toxicities are frequently observed with the PCV regimen in clinical practice. It might be preferable to adjust doses from the start of chemotherapy to improve tolerability or consider alternative chemotherapy, particularly in older patients with LGG.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Glioma; Humans; Incidence; Ireland; Lomustine; Male; Neoplasm Grading; Procarbazine; Retrospective Studies; Time Factors; Vincristine
PubMed: 33557783
DOI: 10.1186/s12885-021-07809-5