Local relapses of head and neck
tumors are not often eligible for surgical and/or
radiotherapy retreatment, and the efficacy of systemic
chemotherapy is poor. A greater accumulation and efficacy of anticancer drugs with lower systemic toxicity is theoretically obtained with intratumoral
chemotherapy. In experimental studies,
epinephrine has been shown to increase the concentration and antitumor effect of intratumoral
cisplatin. Fourteen patients with locally recurrent head and neck
tumors (median age, 58.7 years) were included in this phase 2 trial. Recurrent
tumors (
squamous cell carcinomas) were located on the tongue, oral pharynx, or cervical nodes. Prior
therapy was surgery and/or
radiotherapy with or without intravenous
chemotherapy. Inclusion criteria included an Eastern Cooperative Oncology Group/World Health Organization performance status of 0, 1, or 2, an anticipated survival of >3 months, adequate cardiac, kidney, liver, and bone marrow function, and no coagulopathy or carotid invasion. Fifty intratumoral
injections of
cisplatin-
epinephrine (average, 3.6
injections per patient; range, 1 to 5
injections) were given to the 14 patients from November 1998 to July 2000. Patients were treated with
cisplatin (1 mg/mL; maximum dose, 50 mg) at an injection volume corresponding to the
tumor volume (1 mL/cm3 of
tumor; maximum volume, 50 mL).
Epinephrine was added at a concentration of 0.02 mg/mL. Intratumoral
injections were repeated every 2 to 3 weeks at different locations in the
tumors to obtain a homogeneous distribution.
Tumor response was evaluated by clinical examination and computed tomography. Eight objective responses were registered among the 14 patients. Four were complete responses, and 4 were partial responses. The average time to
disease progression was 11.5 +/- 8.9 weeks. Local adverse effects were transient
pain, swelling, and
erythema at the site of the injection. No nephrotoxicity, neurotoxicity, or
ototoxicity was observed. Intratumoral injection of
cisplatin and
epinephrine in an aqueous
solution has a definite antitumor activity in recurrent
head and neck cancer with acceptable local tolerance and no major systemic toxic effects except for transient
tachycardia and
high blood pressure at the time of injection.