Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkin's lymphoma.
BACKGROUND
The purpose of this study was to assess the efficacy and safety of ISIS 3521, an antisense phosphorothioate oligonucleotide to protein kinase C alpha in patients with relapsed low-grade non-Hodgkin's lymphoma (NHL).


METHODS
Twenty-six patients received ISIS 3521 (2 mg/kg/day) as a continuous infusion over 21 days of each 28-day cycle.


RESULTS
The median age of the patients was 53 years (range 37-77). Histological subtypes were low-grade follicular lymphoma (n = 22) and B-cell small lymphocytic lymphoma (n = 4). Twenty-one (81%) had stage III/IV disease. The median number of previous lines of chemotherapy was two (range one to six). A total of 87 cycles of ISIS 3521 were administered. Twenty-three patients were assessable for response. Three patients achieved a partial response. No complete responses were observed. Ten patients had stable disease. Grade 3-4 toxicity was as follows: neutropenia (3.8%) and thrombocytopenia (26.9%).


CONCLUSIONS
ISIS 3521 has demonstrated anti-tumour activity in patients with relapsed low-grade NHL. There may be a potential role for this agent in combination with conventional chemotherapy for advanced low-grade lymphoma, and further trials are warranted.
Royal Marsden Hospital, London, UK.
S
S
Rao
D
D
Watkins
D
D
Cunningham
D
D
Dunlop
P
P
Johnson
P
P
Selby
B W
BW
Hancock
C
C
Fegan
D
D
Culligan
S
S
Schey
T C M
TC
Morris
T
T
Lissitchkov
J W
JW
Oliver
J T
JT
Holmlund
D000328:Adult; D000368:Aged; D005260:Female; D005334:Fever / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D020319:Oligodeoxyribonucleotides, Antisense / Q000009:adverse effects / Q000627:therapeutic use*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051571:Protein Kinase C-alpha; D013873:Thionucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D020319:Oligodeoxyribonucleotides, Antisense; D013873:Thionucleotides; C108494:ISIS 3521; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha