Phase II study of rhizoxin in squamous cell head and neck cancer

J Verweij,T Gil,A Te Velde,G Catimel,P Schöffski,Phm De Mulder,J Wanders

doi:10.1038/bjc.1996.69

Abstract

To test the anti-tumour activity of rhizoxin in recurrent and/or metastatic squamous cell head and neck cancer, we performed a phase II study. Eligibility required histologically proven squamous cell head and neck cancer. Patients could only have received one prior chemotherapy. Patients were entered if WHO PS was < or = 2 and organ functions were normal. Treatment consisted of rhizoxin 1.5-2.0 mg m-2 i.v. bolus injection once every 3 weeks. Thirty-two patients entered the study. All were eligible, 31 were evaluable for toxicity and 25 for response. Toxicity mainly consisted of pain at the tumour site and leucocytopenia. Mild asthenia and stomatitis were also observed. Two objective partial responses, lasting 7.5 and 3.5 months, were seen. Rhizoxin at this dose and schedule has minor activity in recurrent and/or metastatic squamous cell head and neck cancer.

Highlights

The most intriguing side-effect of rhizoxin was a severe pain at the tumour site, that could hardly be controlled by intravenous morphines
In the presently reported phase II study, treatment was initially poorly tolerated due to a remarkably severe pain, occurring at tumour sites previously treated with radiotherapy and unrelievable by any analgetic treatment, including intravenous morphines, but reduction of the starting dose resulted in complete disappearance of this side-effect
This side-effect was not noted in patients who had undergone previous radiotherapy for other diseases, but in most of these diseases radiation doses were lower than the common dose used in the treatment of head and neck cancer

Summary

Patients and methods

Eligibility criteria included histologically or cytologically verified, uni- or bidimensionally measurable, locally advanced, unresectable or metastatic squamous cell carcinoma of the head and neck, WHO performance status < 2, age > 18 years; and adequate bone marrow (WBC > 4000 ul platelets,> 100 000 MIl-1), hepatic and renal function. The resulting solution contained: rhizoxin 1 mg ml-' in 40% propylene glycol (v/v), 10% ethanol (v/v) in sterile water for injection. Rhizoxin was administered at a dose of 2 mg m-2 by a single bolus i.v. injection once every 3 weeks. It was to be administered directly into the vein, not into a running drip, as it precipitates in saline and dextrose solutions. Treatment had to be delayed by 1 week if WBC and platelets at the scheduled day of retreatment were < 3.0 x 109 l-l and/or < 100 x 19 1- I respectively In this case the course was to be given at 75%. Tumour measurements and the related diagnostics were repeated every two courses

Evaluation

Results

Discussion