Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy.
OBJECTIVE
Thalidomide has demonstrated a remarkable efficacy in the treatment of multiple myeloma but its use may cause several toxicities. We have investigated the common and rare side-effects, especially analysing peripheral neuropathy, in order to optimise the thalidomide dose for minimizing this harmful side-effect.


METHODS
Fifty-nine patients were treated with thalidomide alone or combined with oral melphalan. The median age was 69 yr. The initial dose of thalidomide was 100 mg/day increasing weekly by 100 mg increments until a maximum dose of 400 mg was attained. Melphalan was administered at a dose of 0.20 mg/kg/d for 4 d every 28 d.


CONCLUSIONS
Nearly one-fourth of patients discontinued thalidomide because of toxicity. Constipation (71%), somnolence (36%) and fatigue (20%) were the most common side-effects and they were not dose dependent. Peripheral neuropathy occurred in 39% of patients and a thalidomide median daily dose of more than 150 mg was significantly associated with higher frequency and actuarial risk of peripheral neuropathy without improving the response rate. Deep venous thrombosis was observed in 7% of patients and other side-effects were rare. In patients with advanced multiple myeloma we found that a thalidomide daily dose of 150 mg minimizes peripheral neuropathy without jeopardizing response and survival.
Offidani
Massimo
M
Clinica di Ematologia, University of Ancona, Ancona, Italy. m.offidani@ao-umbertoprimo.marche.it
Corvatta
Laura
L
Marconi
Monica
M
Malerba
Lara
L
Mele
Anna
A
Olivieri
Attilio
A
Brunori
Marino
M
Catarini
Massimo
M
Candela
Marco
M
Capelli
Debora
D
Montanari
Mauro
M
Rupoli
Serena
S
Leoni
Pietro
P
D000368:Aged; D000369:Aged, 80 and over; D003248:Constipation / Q000139:chemically induced; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control; D011336:Probability; D013792:Thalidomide / Q000008:administration & dosage / Q000633:toxicity*; D020246:Venous Thrombosis / Q000139:chemically induced
D013792:Thalidomide; D008558:Melphalan