Low-dose hyperradiosensitivity: is there a place for future investigation in clinical settings?
OBJECTIVE
In vitro radiation doses of below 0.5 Gy have been shown to be more effective than higher doses per unit dose in killing clonogenic cells of many epithelial tumor cell lines. This phenomenon is known as low-dose hyperradiosensitivity. Preclinical studies have now suggested that there is synergism between chemotherapy and low-dose fractionated radiotherapy (LD-FRT). To test the clinical efficacy of this approach, we prospectively evaluated concurrent palliative chemotherapy and LD-FRT in patients with various types of epithelial tumors.


METHODS
Patients suffering from relapses or metastases of epithelial tumors were scheduled to receive concurrent LD-FRT (two fractions of 0.4 Gy per day) and chemotherapy. Radiologic assessments were performed after three cycles of chemotherapy plus LD-FRT.


RESULTS
Between June 2006 and October 2007, 12 patients with lung cancer, 7 patients with head-and-neck tumors, 2 patients with breast cancer, and 1 patient with esophageal carcinoma, for a total patient population of 22, underwent concomitant LD-FRT and chemotherapy. All patients but 3 (86%) had received previous treatments for their cancer. The median total dose of LD-FRT delivered was 800 cGy (range, 320-1280 cGy). The overall response rate was 45% (42% in previously treated patients). Grade 3-4 hematologic toxicities (Radiation Therapy Oncology Group ratings) were observed in 2 patients. At a median follow-up of 6.5 months, however, no local toxicity was observed.


CONCLUSIONS
In our experience, concurrent LD-FRT and chemotherapy was well tolerated. Because the response rate seems promising, prospective Phase II studies of the strategy are now under way.
Valentini
Vincenzo
V
Radiotherapy Department, Policlinico Universitario A.Gemelli, Catholic University, Rome, Italy.
Massaccesi
Mariangela
M
Balducci
Mario
M
Mantini
Giovanna
G
Micciché
Francesco
F
Mattiucci
Gian Carlo
GC
Dinapoli
Nicola
N
Meduri
Bruno
B
D'Agostino
Giuseppe Roberto
GR
Salvi
Giovanna
G
Nardone
Luigia
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D010166:Palliative Care / Q000379:methods*; D000068437:Pemetrexed; D011446:Prospective Studies; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D055815:Young Adult
D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil