Primary central nervous system non-hodgkin's lymphoma: Survival advantages with combined initial therapy?

O’Neill, Brian Patrick; O’Fallon, Judith R.; Earle, John D.; Colgan, Joseph P.; Brown, Loren D.; Krigel, Robert L.

doi:10.1016/0360-3016(95)00207-f

Cited by 132 publications

(41 citation statements)

References 44 publications

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“…In the papers considered, all three patients receiving CHOP at failure died within 8 months. Also as first-line therapy, CHOP or cyclophosphamide, doxorubicin, vincristine and dexamethasone (CHOD) regimens were ineffective (Lachance et al, 1994;OÕNeill et al, 1995;Bessell et al, 1996;Glass et al, 1996;Schultz et al, 1996). A salvage treatment schedule should include drugs that can cross the BBB and, in particular, agents with some efficacy as primary treatment, such as high-dose methotrexate, cytarabine, vincristine, procarbazine or nitrosureas (Kawakami et al, 1985;Di Marco et al, 1986;McLaughlin et al, 1988;Chamberlain and Levin, 1990;De Angelis et al, 1992;Boiardi et al, 1993;Glass et al, 1994;Bessel et al, 1996;Freilich et al, 1996;Reni et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Second-line treatment for primary central nervous system lymphoma

1999

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Summary Failure after first-line treatment was reported in 35-60% of immunocompetent patients with primary central nervous system lymphoma (PCNSL). There are currently no reports focusing on salvage therapy. This review analyses prognostic factors and the efficacy of salvage therapy by focusing on data from papers reporting results of first-line treatment in 355 cases. The study group consisted of 173 patients presenting treatment failure. The interval between failure and death (TTD) was compared for age at relapse (≤60 vs >60 years), type of failure (relapse vs progression), time to relapse (≤12 vs >12 months) and salvage treatment (yes vs no). Median TTD was similar in younger and older patients (P = 0.09). Relapsed patients had a longer TTD than patients with progressive disease (P = 0.002). Early relapse led to a shorter TTD than late relapse (P = 0.005). Median TTD was 14 months for patients who underwent salvage therapy and 2 months for untreated cases (P < 0.00001). A multivariate analysis showed an independent prognostic role for salvage therapy and time to relapse. Age and type of failure had no predictive value. Salvage therapy significantly improves outcome and, possibly, quality of life. As many different treatments were used conclusions cannot be made regarding an optimal treatment schedule.

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Section: Discussionmentioning

confidence: 99%

Second-line treatment for primary central nervous system lymphoma

1999

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“…CHOP appears to be as effective as any other combination [16]. CHOP also provides high initial response rates in PCNSL, though with short response durations, early multifocal recurrences, and no apparent benefit over WBRT alone as initial therapy [19,20]. Similarly, pre-irradiation CHOD has no benefit over WBRT [21].…”

Section: Discussionmentioning

confidence: 99%

“…Despite the shortcomings of this study, it is clear that MCHOD has activity in PCNSL, though the lack of response in four patients and the short response duration in some others suggests incomplete therapy of intraparenchymal tumor foci. We believe that MTX provided much of the anti-neoplastic activity, with CHOD only contributing to the responses seen in larger mass lesions [17,[19][20][21]. MCHOD does not appear to be superior to HDMTX monotherapy, achieving lesser or similar response durations with greater toxicity.…”

Section: Discussionmentioning

confidence: 99%

Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (MCHOD)

et al. 1996

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Prior studies have suggested that pre-irradiation methotrexate (MTX)-based chemotherapy improves duration of response and survival in primary central nervous system lymphoma (PCNSL). To circumvent the potential emergence of drug resistance, we combined high-dose MTX with agents highly active against systemic lymphoma. Patients received three week cycles of CHOD (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 [2 mg maximum] on day 1; dexamethasone 10 mg/m2 days 1-5), and MTX (3.5 gm/m2) with leucovorin rescue on day 8 (or on recovery from the CHOD nadir). Whole brain irradiation (WBRT) was planned after at least three cycles. Eighteen patients were treated. Complete responses were seen in eleven patients, and partial responses in three. Four progressed during therapy, three succumbing to progressive disease and one subsequently responding to WBRT. Response duration was 37.5 months in those responding to therapy. The time to progression for all eighteen patients was 19.5 months. Medial survival was 25.5 months. Disease-free survival was 50% at 38 months in MCHOD responders. Grade 3 or 4 myelotoxicity was seen in 19 of 50 cycles. There were three instances of neutropenic fever, three of azotemia, two of deep vein thrombosis, and one each of community-acquired pneumonia, intracranial hemorrhage, superior vena cava syndrome, and hepatotoxicity. Late radiation-related toxicities were seen in two patients. Pre-irradiation MCHOD has activity against PCNSL, but appears to be no better than MTX monotherapy and has greater toxicity.

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“…The study by Balmaceda et al [2] with a high proportion of CSF examinations at the start of therapy as well as at the time of recurrence showed that leptomeningeal relapse, with 41%, was quite common and that meningeal recurrence was reduced in patients who received treatment that included the leptomeninges. A high risk of meningeal relapse was also found in other series, but with lower proportion of CSF examinations at diagnosis [13,38].…”

Section: Introductionmentioning

confidence: 64%