Matulane (procarbazine hydrochloride)

Procarbazine induces a higher mutation burden and novel mutational signatures in patients with Hodgkin lymphoma treated with eBEACOPP and their germline DNA, raising concerns for the genomic health of survivors of Hodgkin lymphoma and hereditary consequences for their offspring. However, replacing procarbazine with dacarbazine appears to mitigate gonadal and stem-cell toxicity while maintaining similar clinical efficacy.

Despite advances in treatment, the median survival of patients with GBM is only 15 months. This case highlights the potential of immunotherapy with PD-L1 checkpoint inhibition in improving outcomes for LFS-associated GBM patients. https://thejns.org/doi/10.3171/CASE24539.

The patient experienced tumor pseudoprogression/progression after three cycles of maintenance temozolomide/TTFields therapy and again after a further two cycles of procarbazine/CCNU/TTFields therapy, and was then switched to CCNU/TTFields therapy. This patient case is reflective of the EF-14 study outcome using TTFields therapy beyond first progression concomitantly with chemotherapy. The observations from this case suggest that TTFields therapy concomitant with CCNU is a valuable treatment modality in patients with GBM, in this context.

The beneficial impact of adding chemotherapy to radiotherapy (PCV: procarbazine, lomustine, vincristine) has also been demonstrated. In grade 4 glioblastoma multiforme (GBM), wild-type isocitrate dehydrogenase (IDH) status showed the best treatment outcomes with temozolomide (TMZ) in patients with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation...Bevacizumab (BEV) monotherapy can improve progression-free survival and maintain the initial quality of life. Despite advancements in GBM treatment, outcomes remain unsatisfactory, with a median survival of 14-16 months. Further research is still needed regarding the systemic treatment of central nervous system gliomas.

Adjuvant radiation and PCV are associated with improved PFS over radiation with TMZ in patients with grade 3 molecularly defined oligodendrogliomas, and all-grade patients treated with PCV trended towards decreased risk of recurrence and progression. These results highlight the importance of ongoing clinical trials investigating these treatments.

In patients with newly diagnosed O3IDHmt/Codel from the POLA cohort, first-line PCV/RT was associated with better OS outcomes compared with TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.

This is the first reported case of isolated optic nerve involvement with a durable response to chemotherapy. This case emphasizes the importance of considering malignancy and maintaining a low threshold for optic nerve biopsy in patients with atypical cases of severe steroid-refractory vision loss with enhancement or enlargement of the optic nerve on MRI. Standard chemotherapy regimens for PCNSL can potentially achieve a curative response in these patients.

P1, N=20, Recruiting, Ono Pharmaceutical Co. Ltd

P3, N=305, Active, not recruiting, Alliance for Clinical Trials in Oncology | Recruiting --> Active, not recruiting

P1/2, N=118, Recruiting, Institut Curie | Trial completion date: Jan 2031 --> Feb 2035 | Trial primary completion date: Jan 2024 --> Feb 2025

P2, N=146, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

The carboplatin and vincristine (CV) combination stands as a standard systemic therapy for PLGG, varying in dosage and administration between North America and Europe...Vinblastine has emerged as another effective regimen with minimal toxicity. TPCV, a regimen combining thioguanine, procarbazine, lomustine, and vincristine, was compared to CV in a Children's Oncology Group trial, showing comparable outcomes, but more toxicity. Vinorelbine, temozolomide, and metronomic chemotherapy have also been explored, with varied success rates and toxicity profiles...The landscape of chemotherapy in PLGG is evolving, with a growing focus on molecular subtyping and targeted therapies. Understanding the role of chemotherapy in conjunction with novel treatments is crucial for optimizing outcomes in pediatric patients with low-grade gliomas.

Induction therapy consistedof methotrexate, vincristine, procarbazine (MVP) with (40...1%) rituximab (R-MVP)... We observed a significant proportion of "high-risk" PCNSL characterized by dismal prognosis and tumorupregulation of immune checkpoints TIGIT and HAVCR2, supporting immune evasion as a disease mechanism. This represents a potential avenue for integrating immunotherapy into existing treatment regimens.

P3, N=1500, Active, not recruiting, University of Cologne | Recruiting --> Active, not recruiting

P3, N=1202, Completed, University College, London | Active, not recruiting --> Completed | Trial completion date: May 2023 --> May 2024

P2, N=208, Recruiting, International Extranodal Lymphoma Study Group (IELSG) | Trial completion date: Oct 2023 --> Dec 2024 | Trial primary completion date: Oct 2023 --> Dec 2024

While recommendations are nuanced and reflect the complexity of the disease, maximum safe resection is typically the first step in treatment, followed by radiotherapy and/or chemotherapy using temozolomide or procarbazine, lomustine, and vincristine. The lack of treatment options is compounded by frequently suboptimal clinical practice, in which patients do not receive adequate therapy after resection, including delayed, shortened, or discontinued radiotherapy and chemotherapy courses due to treatment side effects. These unmet needs will require significant efforts to address, including a continued search for novel treatment options, increased awareness of clinical guidelines, improved toxicity management for chemotherapy, and the generation of additional and more robust clinical and health economic evidence.

P1/2, N=41, Active, not recruiting, Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea | Trial completion date: Oct 2023 --> Oct 2024

P2, N=146, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jun 2026 --> May 2024

265 patients within the cohort completed postoperative radiotherapy, while 141 patients underwent chemotherapy (procarbazine, lomustine, and vincristine, or temozolomide). Of particular importance, molecular sub-classification significantly predicted survival outcomes for IDH, ATRX, and 1p19 co-deletion mutations. Expanding brain tumor epidemiology will benefit assessing the efficacy of regional oncological centers and establishing standards of care.

Radiation therapy and PCV (procarbazine, CCNU, and vincristine) was received by 85 patients, while radiation therapy and temozolomide were administered to 15 patients. Conclusions  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.

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)...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.

P1/2, N=118, Recruiting, Institut Curie | Phase classification: P2 --> P1/2

Bevacizumab was added for presumed pseudo-progression; followed by chemotherapy with procarbazine and lomustine (PC)...Despite early introduction of 2nd-line chemotherapy with temozolomide, his disease continued to progress and he succumbed 1.5 years after initial diagnosis...Both IDH mutation and 1p19q co-deletion were lost in the gliosarcomatous transformation. This tumor did not respond to alkylating agents despite the MGMT promoter-methylated status.

In terms of frontline-treatment, 21 patients (95%) had received HDMTX + procarbazine + vincristine, and rituximab was administered in 73% (16/22) of patients...CONCLUSION Given that only restricted treatment strategies are available for relapse PCNSL patients, our study suggests that nivolumab can be a suitable option for the disease. Further studies are warranted to determine predictive biomarkers for nivolumab treatment given the excellent survival duration in responders.

Chemoradiotherapy with procarbazine, CCNU, and vincristine is recommended for both grade 2 and 3 oligodendrogliomas. However, the risk of radiation-induced neurotoxicity is a concern in long-term survivors, and several clinical trials have tested the efficacy of chemotherapy alone in terms of cognitive function. Since CCNU is not approved in Japan, ACNU-containing regimen as PAV, or temozolomide are commonly used for the tumor.

Eight patients received a third line of treatment: 2 radiotherapy, 4 Bevacizumab, 1 Procarbazine and 1 TMZ. While our patients were older and with lower KPS than the patients in the RCTs the efficacy of TMZ only treatment was comparable with the clinical trials results with mOS of 11/11. 9/8. 3 month in Sheba/NOA08/Nordic patients, PFS of 5/8.

This study revealed that both the S + RT + TMZ and S + RT + PCV regimens might be effective therapies for treating patients with low-grade gliomas. Among these, the S + RT + TMZ regimen seemed to be safer, but might lead to tumor deterioration. In the IDHmt/coder type, the S + RT + TMZ scheme might have a significant advantage. In the IDHmt/noncoder type, the S + RT + PCV scheme might be more dominant, while in the IDHwt type, the S + H - RT and S + TMZ schemes also might be good treatment options.

Case Study: A 54-year-old man was diagnosed with HL mixed-cellularity 202 months ago and was treated with chemotherapy, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for 8 cycles...The patient had another disease progression with a positive Pet-CT 13 months after the second remission, and it was proposed that the treatment be switched to escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), in which he had received 6 cycles... Data supports using pembrolizumab as monotherapy in cases of relapsed HL; nevertheless, in our case, we do not have a sustained response to the therapeutic impact to draw a firm judgment.

The best treatment strategy for elderly PCNSL patients remains unknown. Treatments range from palliative to curative but more toxic therapies, and there is no standardized measure to select patients for the right treatment. This randomized controlled trial will create evidence for the best treatment strategy with the focus on developing a standardized GA to help define eligibility for an intensive treatment approach.

We modified the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone), whereby bleomycin and etoposide were removed and cyclophosphamide dose was reduced, for older patients with co-morbidities. Here we present data from the first 41 patients treated with 'ACOPP' across 3 centres, demonstrating that it can be delivered, with a favourable toxicity profile (TRM 2%) and promising efficacy (2-year PFS and OS, 73% (95% CI: 52-94) and 93% (95% CI: 80-100) respectively).

Long-term follow-up demonstrated that treatment was well tolerated in most patients enrolled in this study, with stable leukoencephalopathy on imaging and stable clinical performance status. Disease recurrence was not observed beyond 2 years after HDC-ASCT consolidation.

MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) is an effective rescue protocol used to re-induce remission, but is associated with gastrointestinal toxicity and can be a less desirable option for patients that previously failed vincristine-containing protocols. MVPP at the prescribed doses resulted in modest and transient clinical benefit, but was well tolerated with no treatment delays or hospitalizations secondary to side effects. Given the minimal toxicity, dose intensification could be considered to improve clinical responses.

We aimed to evaluate the outcome of rituximab, methotrexate, procarbazine, and vincristine (RMPV) chemotherapy in elderly patients with new-onset PCNSL...Patients received five to seven cycles of RMPV plus response-adapted whole-brain radiotherapy (WBRT) and cytarabine...Initial treatment with RMPV chemotherapy was effective in elderly patients with PCNSL. Adjusting the number of courses of RMPV may improve the prognosis of elderly patients with PCNSL, but further verification is necessary.

These studies investigated the omission of consolidation radiotherapy (RT) in patients with a negative interim positron emission tomography (iPET) (ie, Deauville score <3) after chemotherapy (HD16: 2× doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]; HD17: 2× escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP] plus 2× ABVD). Taken together, contemporary HL-directed treatment approaches result in excellent outcomes for patients with newly diagnosed early-stage NLPHL and thus represent valid treatment options. In patients with early-stage favorable NLPHL, consolidation RT appears necessary after 2xABVD to achieve the optimal disease control irrespective of the iPET result.

Anaplastic oligodendroglioma patients treated with postoperative PCV chemotherapy alone occasionally develop T2/FLAIR hyperintensities around the surgical cavity that can wrongly suggest tumour progression. Multimodal imaging and close follow-up should be considered in this situation.

HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.

Upfront first-line chemotherapy is indicated for all features of classical Hodgkin's lymphoma, followed by involved node radiotherapy in early stages; the ABVD protocol (doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine) is the international standard of care. The 7-agent BEACOPP protocol (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine (Oncovin), procarbazine, prednisone) is used in advanced stages in its «escalated» version (BEAesc)...Thus, early PET response evaluation is now essential to adapt the treatment intensity. Despite these major advances, several issues remain, including the management of acute and long-term side effects of first-line treatments, the better options for refractory patients, the place and optimization of radiotherapy, and the place for new therapeutic agents such as the anti-CD30 conjugate antibody (brentuximab vedotin) and PD-1 inhibitors in the first-line treatment setting.

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.

The vast majority of patients are PET 2 negative (Deauville scores of 1–3) after 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Adult trials have studied various approaches, and in general, 2–4 additional cycles of ABVD or 4 cycles of AVD result in more than 90% of patients being disease free at 3 years.4–6 Outcomes in patients who are PET2 positive (Deauville 4–5) are less favorable, though escalation to BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) with the addition of radiotherapy results in improved progression free survival (PFS) compared to continuation of ABVD plus RT.4 A US and Canadian Intergroup trial led by the Children's Oncology Group using a PET adapted approach after 2 cycles of ABVD recently opened and will randomize patients to standard therapy versus BV plus nivolumab...For patients who are BV naïve, brentuximab plus nivolumab is highly active with high overall and complete response rates.11 More recently, a phase 2 study demonstrated excellent outcomes in patients treated with pembrolizumab plus gemcitabine/vinorelbine/doxil.12 S9 The current standard of care is consolidation with high dose chemotherapy with stem cell rescue (ASCT) in responding patients...Single center studies using intensified regimens showed better outcomes compared to CHOP.13 The introduction of rituximab led to improved PFS of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) compared to CHOP alone...In addition, survivorship issues are paramount. Integrated care with psychosocial support, discussion of fertility preservation and monitoring for late effects are crucial for optimal outcomes both medically and with respect to quality of life.