Results of randomised phase II studies comparing S16020 with methotrexate in patients with recurrent head and neck cancer.
BACKGROUND
The purpose of this study was to carry out two randomised phase II trials of S16020, a new olivacine derivative, tested as a single agent in patients with recurrent head and neck cancer, using methotrexate as the control arm to validate the results.


METHODS
S16020 at either 80 or 100 mg/m2 was administered as a 3-h infusion every 3 weeks. Methotrexate, 40 or 50 mg/m2, was given by bolus injection, weekly for a minimum of 6 weeks. In total, 36 patients were entered in the randomised studies (25 in an initial study, 11 in a confirmatory study) of whom 24 received S16020 and 12 received methotrexate.


RESULTS
A scheduled interim analysis showed one patient having a non-confirmed objective response with S16020 and three patients having a confirmed objective response with methotrexate. In the methotrexate group, there were no patients with severe non-haematological toxicity. With S16020, there was a high incidence of severe non-haematological toxicities, including asthenia, oedema of the face, oedema and pain at the tumour sites and erythematous rash; consequently, both studies were stopped.


CONCLUSIONS
Both studies were stopped due to the poor anticipated benefit/risk ratio for S16020, although time to progression and overall survival time were similar in both treatment arms.
Pivot
X
X
Service d'Oncology, CHU J. Minjoz, Besançon, France. xpivot@chu-besancon.fr
Awada
A
A
Gedouin
D
D
Kerger
J
J
Rolland
F
F
Cupissol
D
D
Caponigro
F
F
Comella
G
G
Lopez-Pousa
J J
JJ
Guardiola
E
E
Giroux
B
B
Gérard
B
B
Schneider
M
M
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D004487:Edema / Q000209:etiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D002227:Carbazoles; C117470:NSC 659687; D011725:Pyridines; D008727:Methotrexate