Dexamethasone, high-dose cytarabine, and oxaliplatin (DHAOx) as salvage treatment for patients with initially refractory or relapsed non-Hodgkin's lymphoma.
BACKGROUND
Dexamethasone. cytarabine (ara-C), and cisplatin (DHAP) can be used effectively to treat patients with non-Hodgkin's lymphoma (NHL). We hypothesized that substitution of cisplatin by oxaliplatin (L-OHP) could result in less toxicity and greater efficacy. L-OHP is active in patients with lymphoma. It produces mild myelosuppression and is devoid of renal toxicity. We report on a phase II study of dexamethasone, high-dose ara-C, and L-OHP (DHAOx) used to treat patients with NHL who were previously treated with chemotherapy.


METHODS
Fifteen patients were given DHAOx. They had failed to achieve a CR with initial chemotherapy or had recurrent disease. DHAOx consisted of dexamethasone, 40 mg/day (days 1 to 4): L-OHP, 130 mg/m2 (day 1); and ara-C, 2,000 mg/m2 every 12 h (day 2). Treatment was repeated every 21 days.


RESULTS
Patients received a median of four courses of DHAOx. Myelosuppression and transient sensory peripheral neuropathy were the most prominent toxic effects. Serum creatinine levels did not increase in patients with normal renal function, nor in patients who had renal impairment before DHAOx. The median follow-up time from the start of DHAOx treatment was 17 months. Eight patients (53%) achieved a CR, and three patients (20%) had a PR. Responses were achieved by patients with lymphomas of various histologies that included mainly the follicular subtype, and by patients with and without resistance to prior chemotherapy. None of the eight responders have relapsed from CR at 4+. 6+, 14+, 15+, 19+, 20+, 24+, and 24+ months. They had various types of therapy after DHAOx. Disappearance of molecular markers was observed in all four patients who achieved a CR and whose tumor cells carried molecular abnormalities.


CONCLUSIONS
DHAOx possesses characteristics of toxicity which compare favorably to those reported with DHAP, and it is useful as a salvage treatment for patients with NHL. Larger studies are required to establish the therapeutic potential of the regimen.
Machover
D
D
Department of Hematology and Oncology and the Institut du Cancer et d'Immunogénétique (ICIG), Hospital Paul Brousse, Villejuif, France. david.machover@pbr.ap-hop-paris.fr
Delmas-Marsalet
B
B
Misra
S C
SC
Gumus
Y
Y
Goldschmidt
E
E
Schilf
A
A
Frénoy
N
N
Emile
J F
JF
Debuire
B
B
Guettier
C
C
Farrokhi
P
P
Boulefdaoui
B
B
Norol
F
F
Parquet
N
N
Ulusakarya
A
A
Jasmin
C
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D012008:Recurrence; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone