High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study

Illerhaus, Gerald; Marks, Reinhard; Müller, Fabian; Ihorst, Gabriele; Feuerhake, Friedrich; Deckert, Martina; Ostertag, Christoph B.; Finke, Jürgen

doi:10.1093/annonc/mdn628

Cited by 112 publications

(69 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it is possible that selection bias negatively impacted survival data in our study because many older patients with severe comorbidities participated in the study. Similar to what has been shown for the combination of HD-MTX/lomustine/procarbazine [12], our patient population falls into two subgroups: (1) the larger group of patients not at all responding to chemotherapy or rapidly progressing after a very short period of response and (2) the smaller group of patients deriving notable benefit from chemotherapy with extended PFS and a high potential for long-term survival (four of 17 patients surviving relapse-free for substantially more than two years). Our MGMT promoter methylation data is compatible with the notion that sustained response and prolonged survival are not possible in the presence of a non-methylated MGMT promoter (PFS 1-3 months).…”

Section: Discussionsupporting

confidence: 81%

“…CR rate (47%), mPFS (5 months) and mOS (21 months) compare well to presumably more toxic regimens such as chemotherapy on a HD-MTX, lomustine and procarbazine base (CR rate 42-47%, mPFS 5.9-6.8 months and mOS 14.3-15.4 months) [11,12]. Survival with TMZ monotherapy is somewhat shorter than with a combination of HD-MTX and TMZ (CR 55%, mPFS 8 months, mOS 35 months) [13].…”

Section: Discussionmentioning

confidence: 72%

See 1 more Smart Citation

Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status

et al. 2009

View full text Add to dashboard Cite

This retrospective series explores temozolomide monotherapy in elderly patients with primary CNS lymphoma (PCNSL) and severe comorbidities. In 17 patients (62-90 years old), complete response rate was 47%, median progression-free survival was five months and median overall survival was 21 months. Five of 17 patients (29.4%) had prolonged responses for at least 12 months and survived for more than 24 months. Three of these patients had a methylated O 6 -methylguanine-DNA methyltransferase (MGMT) promoter while the MGMT status was not assessable in the remaining two patients. Temozolomide monotherapy appears to be effective in a subgroup of elderly PCNSL patients and deserves further evaluation.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 72%

Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Ocular lymphoma, reported to occur in 3%-14% of PCNSL patients, 25,30 was found in 4 of 66 patients in our study (6%). None of them completed treatment due to poor clinical condition, toxicity or progressive disease.…”

Section: Discussionsupporting

confidence: 38%

“…Our approaches of de-escalating induction and introduction of maintenance therapy have provided results which are among the most favorable ever reported in elderly PCNSL patients. 5,30,31,32 Thus, moving the focus to the maintenance phase seems to indicate that temozolomide maintenance has been of benefit regarding sustained remission, since relapse after achieving CR occurred in only 5 of 18 elderly patients (28%) as compared to 17 of 27 patients (63%) in the younger subgroup who did not receive maintenance treatment. On the other hand, the induction regimen applied in the elderly subgroup was still too toxic, given that 3 of 4 treatment-related deaths occurred in this age group.…”

Section: Discussionmentioning

confidence: 99%

Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by The Nordic Lymphoma Group

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Again, various compounds have been added to MTX and assessed in smaller trials. The combination of MTX with procarbazine and lomustine resulted in a median OS of 15.4 months [69] which was only moderately changed to 17.5 months when rituximab was added in a subsequent trial [70]. A polychemotherapy regimen and additional intrathecal chemotherapy yielded a median OS of 14.3 months in a study with 50 PCNSL patients who had a median age of 72 years [71].…”

Section: Elderly Patientsmentioning

confidence: 99%

Treatment of Primary CNS Lymphoma

Roth

Stupp

Eisele

2013

Curr Treat Options Neurol

View full text Add to dashboard Cite

OPINION STATEMENT: Primary central nervous system lymphoma is a particular challenge in clinical neuro-oncology. In contrast to most other malignant brain tumors, it may be considered a curable disease at least in younger patients who can tolerate intensive treatment regimens. Yet, therapeutic progress has been limited with little measurable improvement in outcome over the last two decades, mainly due to the low incidence of this tumor, which impedes the execution of large randomized clinical trials, and the failure of most large cooperative groups to conduct such trials. Whenever possible, high-dose methotrexate (HD-MTX) is the backbone of the therapeutic regimen. Response rates can be increased by the addition of second agents like ifosfamide or cytarabine, however, their impact on overall survival is less clear. Similarly, the use of the anti-CD20 antibody rituximab, commonly used in the treatment of B cell lymphomas outside the CNS, remains controversial and has not been examined in adequate clinical trials. The prognosis of patients, who do not qualify for HD-MTX-based chemotherapy, is considerably poorer. Radiation therapy is an active treatment with high response rates but does typically not result in long-lasting remissions. It remains an important therapeutic option as a salvage therapy in patients progressing on or no longer responding to HD-MTX-based treatment. The combination of HD-MTX and radiation therapy does not prolong overall survival. It is associated with significant neurotoxicity, and it should be avoided. Another matter of debate is whether consolidation therapy by other means, such as high-dose chemotherapy followed by stem cell support, is the most promising regimen. Given these numerous uncertainties, neuro-oncologists should strive for a treatment of PCNSL patients within clinical trials to allow for the development of improved therapeutic regimens. therapy does not prolong overall survival, is associated with significant (neuro-)toxicity and should be avoided. Whether consolidation therapy by other means such as highdose chemotherapy followed by stem cell support is the most promising regimen, is another matter of debate. Given these numerous uncertainties, neuro-oncologists should strive for a treatment of PCNSL patients within clinical trials to allow for the development of improved therapeutic regimens.

show abstract

High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study

Abstract: The combination of high-dose MTX with procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy. Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients.

Cited by 112 publications

References 34 publications

Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status

Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status

Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by The Nordic Lymphoma Group

Treatment of Primary CNS Lymphoma

Contact Info

Product

Resources

About