Phase I-II study of pegylated liposomal cisplatin (SPI-077) in patients with inoperable head and neck cancer.
BACKGROUND
Concomitant chemoradiotherapy (CCRT) for squamous cancers of the head and neck (SCCHN) improves survival but increases toxicity. Pegylated liposomes localise to solid cancers and may deliver radiosensitizing agents preferentially to tumour tissue, potentially improving the therapeutic ratio of CCRT.


METHODS
A phase I-II trial of pegylated liposome encapsulated cisplatin (SPI-077) was conducted in 18 patients with treatment-naive locally advanced, inoperable SCCHN. The first 10 patients received 2 cycles of 200 mg/m2, and the next 8 received 260 mg/m2, every 3 weeks before commencing radical radiotherapy (RT).


RESULTS
Only 2 of 18 (11%) patients had partial responses to SPI-077 with 2 responses in 29 (6.9%) evaluable sites. SPI-077 was tolerated well with no haematological, renal, hepatic or neurological toxicities. Nausea and vomiting were minimal. There were no drug-related delays in the delivery of RT. RT-induced mucosal and cutaneous toxicity were not significantly increased.


CONCLUSIONS
SPI-077 is essentially inactive against SCCHN and, in its present formulation, does not merit further evaluation as induction chemotherapy or as part of a CCRT approach.
Harrington
K J
KJ
ICRF Laboratory of Molecular Therapy, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, UK. harrington.kevin@mayo.edu
Lewanski
C R
CR
Northcote
A D
AD
Whittaker
J
J
Wellbank
H
H
Vile
R G
RG
Peters
A M
AM
Stewart
J S
JS
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C422270:SPI-77, liposomal; D002945:Cisplatin