A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory lymphomas.
BACKGROUND
We have previously reported that combination chemotherapy based on the drugs cytarabine/platinum is effective in recurring lymphomas. In this phase II study, we prospectively studied a combination regimen of mesna/ifosfamide, mitoxantrone and etoposide (MINE) in patients with recurring lymphoma who had already received cytarabine/platinum but did not respond to the treatment.


METHODS
48 patients received MINE at the following doses: mesna 1.33 g/m2 i.v. daily x 3, and 500 mg p.o. daily 4 hours after each i.v. dose; ifosfamide 1.33 g/m2 i.v. daily, given concurrently with mesna, x 3 d; mitoxantrone 8 mg/m2 i.v. on day 1; and etoposide 65 mg/m2 i.v. daily x 3. Treatment cycles were 21-28 days apart, depending on patients' blood counts, with a maximum number of 6 cycles in responding patients. The histologic grade of the lymphomas according to the Working Formulation was low in 8 patients and intermediate in 40 patients. In the latter group, 12 were transformed from low grade.


RESULTS
Overall, 48% of the patients responded, with 21% having a complete response (CR), and 27% having a partial response (PR). The median survival time was 9 months, and the median follow-up of survivors is 51 months at this writing. Median time to treatment failure was 12 months for patients with complete responses, and 5 months for patients with partial responses. The most serious complication was myelosuppression, with 2 deaths resulting from neutropenic infection.


CONCLUSIONS
The MINE regimen induced responses in a moderate fraction of patients after their prior exposure to cytarabine/platinum salvage therapy, indicating there is no absolute cross resistance between these drug regimens.
Rodriguez
M A
MA
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston, USA.
Cabanillas
F C
FC
Hagemeister
F B
FB
McLaughlin
P
P
Romaguera
J E
JE
Swan
F
F
Velasquez
W
W
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D015080:Mesna / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D010984:Platinum / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D017211:Treatment Failure
D003561:Cytarabine; D010984:Platinum; D005047:Etoposide; D008942:Mitoxantrone; D015080:Mesna; D007069:Ifosfamide