Treatment Of Advancedstage Disease

Several studies have defined the standards of care for patients with advanced-stage CHL and are discussed in Chapter 73. Based on the results of these studies, most patients in the United States are treated with ABVD, Stanford V (doxorubicin, vinblastine, vincristine, bleomycin, mechlorethamine, etoposide, and pred-nisone), or, less often, BEACOPP (bleomycin, etopo-side, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) with or without RT to sites of initially bulky disease.63-65 LPHL accounted for only 1-5% cases so the conclusions from these studies are not necessarily applicable to NLPHL patients.

On the basis of limited data and primarily individual institutional preferences, the National Comprehensive Cancer Network (NCCN) guidelines suggest that patients with advanced (as well as early) stage NLPHL requiring chemotherapy should receive "alkylator-based" regimens.62 Actually, very little published data are available on the most appropriate chemotherapy regimen in patients with NLPHL. In one retrospective study, 8 of 12 LPHL patients treated initially or at first relapse with MOPP or a MOPP-like regimen achieved a durable first or second complete remission, but only 2 of 6 patients treated initially or at first relapse with ABVD or EVA (etoposide, vinblastine, and doxorubicin) achieved a durable first or second complete remis-sion.30 A recently published study from the same institution retrospectively compared outcome of MOPP versus ABVD as salvage therapy in 100 HL patients who relapsed between 1980 and 1997 following primary RT.66 Ninety-seven of the patients were stage I-II, and 10 had NLPHL. They observed no difference in freedom from second relapse or survival between the two groups of patients and no difference in outcome based on histology.

The results from two recent publications suggest that rituximab, an anti-CD20 monoclonal antibody with activity in B-cell NHL, may have a role in the management of patients with NLPHL. These two prospective, phase II trials evaluated the potential efficacy of a standard 4-week course of rituximab in patients with NLPHL. Between May 1999 and March 2002, GHSG enrolled 10 patients (median age 41, range 23-49 years) with NLPHL in first (n = 5), second (n = 2), or third (n = 2) relapse, and a median of 8.5 (range 0.5-21) years after initial diagnosis.67 Five patients had a complete response, four patients had a partial response, and one patient (who had relapsed 6 months after initial diagnosis and soon after completing BEACOPP) progressed. Two of the nine responding patients progressed at 12 months. The other seven patients remained in remission at 9+ to 26+ months. The other study enrolled 22 NLPHL patients (median age 45, range 18-63), who were previously untreated (n = 12) or were in first (n = 6), second (n = 3), or fourth (n = 1) relapse, and a median of 11.9 (range 1-33) years after initial diagnosis and a median of 9 (range 0.4-27) years after the prior treatment.68 The complete and partial response rates were 46% and 54%, respectively. The response duration was relatively short. Six of 12 previously untreated and 3 of 10 previously treated patients relapsed a median of 9 months after the first rituximab infusion. Eight of the nine patients relapsed exclusively at the sites of prior disease. Five of these nine patients had a repeat biopsy. Two of the five patients (including one, who was previously untreated) relapsed with DLBCL.

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