Intravenous melphalan, thalidomide and prednisone in refractory and relapsed multiple myeloma.
OBJECTIVE
Thalidomide combined with conventional chemotherapies including oral melphalan shows significant anti-myeloma activity. To address this issue, feasibility and efficacy of a three drug combination consisting of intravenous (i.v.) melphalan, thalidomide and prednisone [M(i.v.)PT] was evaluated in advanced myeloma patients.


METHODS
Twenty-four advanced myeloma patients were treated with multiple cycles of a regimen consisting of low dose i.v. melphalan (20 mg/m2) at d 1, thalidomide at the dose of 50-100 mg/d given continuously and oral prednisone at the planned dose of 50 mg/d every other day. Intravenous melphalan was administered every fourth month. Median time from diagnosis was 40 months (range: 8-144 months). Fifteen patients (66%) had previously been treated with a combination of thalidomide and dexamethasone or with thalidomide alone.


RESULTS
Overall, on an intent-to treat basis, 14 patients responded: three achieved near complete remission (nCR), seven achieved partial response (PR), four minimal response (MR). Six patients showed stable disease (SD) and four-disease progression. Interestingly, of five patients who had previously progressed while on thalidomide and prednisone, one reached nCR, two PR and one MR. After a median follow up of 14 months, median progression free survival was 9 months. Response duration was longer than that induced by the previous line of treatment in eight patients (33%). Thalidomide-associated toxicity mainly consisted of constipation, tingling and sedation.


CONCLUSIONS
M(i.v.)PT is an effective regimen, which can overcome resistance to thalidomide plus prednisone in advanced myeloma with acceptable toxicity.
Palumbo
Antonio
A
Divisione di Ematologia, l'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Ospedale Molinette, Turin, Italy.
Avonto
Ilaria
I
Bruno
Benedetto
B
Ambrosini
Maria Teresa
MT
Bringhen
Sara
S
Cavallo
Federica
F
Falco
Patrizia
P
Boccadoro
Mario
M
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D013792:Thalidomide; D003907:Dexamethasone; D008558:Melphalan