Accelerated radiotherapy with carbogen and nicotinamide (ARCON) for laryngeal cancer.
OBJECTIVE
Tumor hypoxia and tumor cell repopulation are known factors determining radiation response. Accelerated radiotherapy as a method to counteract cellular repopulation was combined with carbogen (95% O2 + 5% CO2) breathing and oral administration of nicotinamide as a means to improve tumor perfusion and oxygenation. The feasibility, toxicity and clinical effectiveness of this approach as a voice-preserving treatment for carcinoma of the larynx was assessed in a prospective study.


METHODS
Sixty-two patients with stage III-IV laryngeal carcinoma were treated with a schedule of accelerated radiotherapy. The total radiation dose to the primary tumor was 64 Gy and that to the metastatic nodes was 68 Gy delivered in fractions of 2 Gy over 35-37 days. Radiotherapy was combined with carbogen breathing in the initial 11 patients and with both carbogen and nicotinamide administration in the subsequent 51 patients.


RESULTS
After a median follow-up of 24 months, the actuarial local control rate at 2 years was 92%. This is higher than any previous report in the literature for this category of patients. Five patients had a local tumor recurrence and underwent laryngectomy. There was one regional recurrence. Including salvage surgery the loco-regional control rate was 100%. Four patients developed distant metastases and died. The actuarial overall survival rate at 2 years was 85%. Toxicity was increased relative to conventional radiotherapy but was considered as acceptable. One patient underwent laryngectomy for radiation-induced cartilage necrosis.


CONCLUSIONS
These preliminary results indicate that advanced laryngeal cancer can be controlled in a high proportion of patients when treated with accelerated radiotherapy combined with carbogen and nicotinamide. This approach offers excellent possibilities for larynx preservation.
Institute of Radiotherapy, University of Nijmegen, The Netherlands.
J H
JH
Kaanders
L A
LA
Pop
H A
HA
Marres
J
J
Liefers
F J
FJ
van den Hoogen
W A
WA
van Daal
A J
AJ
van der Kogel
D000206:Actuarial Analysis; D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D007825:Laryngectomy; D008207:Lymphatic Metastasis / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010100:Oxygen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D016879:Salvage Therapy; D015996:Survival Rate
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen