title: Combination chemotherapy followed by an immunotoxin (anti-B4-blocked ricin) in patients with indolent lymphoma: results of a phase II study.
abstract: The purpose of this article was to evaluate the antitumor effects of a combination chemotherapy program based on ProMACE (prednisone, methotrexate, doxorubicin [Adriamycin], cyclophosphamide, etoposide) followed by a B cell-specific immunotoxin in the treatment of patients with advanced-stage indolent histology non-Hodgkin's lymphomas. We performed a prospective phase II clinical trial in a referral-based patient population. After confirmation of diagnosis and staging evaluation, 44 patients (10 small lymphocytic lymphoma, 27 follicular lymphoma, 7 mantle cell lymphoma; 30 without prior therapy, 14 previously treated) received six cycles of ProMACE-CytaBOM (cytarabine, bleomycin, vincristine [Oncovin], mechlorethamine) combination chemotherapy (with etoposide given orally daily for five days) followed by a 7-day continuous infusion of anti-B4-blocked ricin immunotoxin at 30 microg/kg/day given every 14 days for up to six cycles. A complete response was achieved in 25 of 44 patients (57%), 21 from the chemotherapy alone, 3 converted from partial to complete response with the immunotoxin, and 1 patient became a complete responder after a surgical procedure to remove an enlarged spleen that was histologically negative for lymphoma. With a median follow-up of 5 years, 14 of 25 complete responders have relapsed (56%); median remission duration was 2 years, and overall survival was 61%. Forty-two percent of the complete responders have been in continuous remission for more than 4 years. The median number of courses of immunotoxin delivered was two usually because of the development of human anti-ricin antibodies. ProMACE-CytaBOM plus anti-B4-blocked ricin does not produce durable complete remissions in the majority of patients with indolent lymphoma. However, the remissions appear quite durable (> 4 years) in about 40% of the complete responders.
authors.affiliation: Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Longo
authors.forename: P L
authors.initials: PL
authors.lastname: Duffey
authors.forename: J G
authors.initials: JG
authors.lastname: Gribben
authors.forename: E S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: B D
authors.initials: BD
authors.lastname: Curti
authors.forename: B L
authors.initials: BL
authors.lastname: Gause
authors.forename: J E
authors.initials: JE
authors.lastname: Janik
authors.forename: V M
authors.initials: VM
authors.lastname: Braman
authors.forename: D
authors.initials: D
authors.lastname: Esseltine
authors.forename: W H
authors.initials: WH
authors.lastname: Wilson
authors.forename: D
authors.initials: D
authors.lastname: Kaufman
authors.forename: R E
authors.initials: RE
authors.lastname: Wittes
authors.forename: L M
authors.initials: LM
authors.lastname: Nadler
authors.forename: W J
authors.initials: WJ
authors.lastname: Urba
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001761:Bleomycin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000401:mortality; D008223:Lymphoma / Q000188:drug therapy* / Q000401:mortality; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000401:mortality; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D012276:Ricin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D018796:Immunoconjugates; D000922:Immunotoxins; C117142:anti-B4 blocked ricin immunoconjugate; D003561:Cytarabine; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D012276:Ricin; D011241:Prednisone; D008727:Methotrexate