Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study.

Abstract

Previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of alternating combination chemotherapy, including vincristine, doxorubicin, alkylating agents, and prednisone (160 patients) was more effective than conventional chemotherapy with melphalan and prednisone (77 patients), and whether the addition of the immunomodulating agent levamisole to maintenance chemotherapy enhanced the survival of patients achieving remission. The treatment groups were well matched for all major factors. The more aggressive chemotherapy was more effective at inducing remission, with a significantly higher proportion of patients achieving at least 75% tumor mass regression (53% with alternating combinations versus 32% with melphalan-prednisone, p = 0.002). Furthermore, the median survival was increased to 43 months with alternating combination chemotherapy as compared to 23 months with melphalan-prednisone (p = 0.004). After six to 12 months of induction therapy, 84 patients achieving remission were rerandomized to receive maintenance chemotherapy alone or with the addition of levamisole. The survival from the start of maintenance therapy was longer in patients receiving the added levamisole than with chemotherapy alone (p = 0.01). These findings support the use of aggressive multiagent chemotherapy for remission induction in patients with advanced-stage multiple myeloma.

Treatment of multiple myeloma according to the extension of the disease: a prospective, randomised study comparing a less with a more aggressive cytostatic policy

“…This suggestion has come from the retrospective analysis of some studies (Harley et al, 1979;Salmon et al, 1983;Cooper et al, 1986;MacLennan et al, 1992) and from a recent meta-analysis (Gregory et al, 1992). None, however, of these studies was originally devised to compare MPH-P with more aggressive regimens in advanced disease.…”

“…Differences could appear with a longer follow-up of a larger group of patients, and we are continuing to follow-up of patients of this series and also recruiting further patients into a protocol started subsequently (MM90). Non-randomised studies (Harley et al, 1979;Cavagnaro et al, 1980;Salmon et al, 1983;Cooper et al, 1986;Riccardi et al, 1986;Kildahl-Andersen et al, 1988;MacLennan et al, 1988;Hjorth et al, 1990;Boccadoro et al, 1991) and their meta-analysis (Gregory et al, 1992) make it unlikely that chemotherapies more aggressive than MPH-P are of benefit in early MM, with the possible notable exception of high-dose chemotherapy followed by bone marrow transplantation in young patients (Garthon et al, 1991).…”

“…Retrospective analyses, as well as a recent meta-analysis (Gregory et al, 1992), suggest that early MM patients do not benefit from aggressive induction chemotherapy (Harley et al, 1979;Cavagnaro et al, 1980;Salmon et al, 1983;Cooper et al, 1986;Riccardi et al, 1986;Kildahl-Andersen et al, 1988;MacLennan et al, 1988;Hjorth et al, 1990;Boccadoro et al, 1991), whereas advanced cases do (Harley et al, 1979;Salmon et al, 1983;Cooper et al, 1986). The question, however, has not been addressed in properly designed, prospective investigations.…”

The treatment of multiple myeloma-an important MRC trial

“…The median duration of remission is of the order of 1-2 years. Initial reports of combination chemotherapy regimens appeared to suggest that higher response rates could be achieved and survival prolonged (Case et al, 1977;Salmon et al, 1983a). Subsequent studies have not supported this conclusion (Cooper et al, 1986;Pavlovsky et al, 1988;Peest et at., 1988;Osterborg et al, 1989;Hjorth et al, 1990), and a recent meta-analysis of trials including nearly 4,000 patients showed no consistent benefit for combination treatments when compared with melphalan and prednisolone (Gregory et al, 1992).…”

Sequential, cycling maintenance therapy for post transplant multiple myeloma

“…Other agents/regimens such as IFNa combinations, 17,20,21 PAIV (prednisone, doxorubicin, azathioprine, vincristine), 22 levamisole, 23 and more recently thalidomide 24 have been studied or are currently under study for use as myeloma maintenance post transplant. To date, however, no particular agent or regimen emerges superior.…”