The therapeutic advantage of combined X-rays and melphalan.
Early skin reactions on mouse feet and delay in growth of a mouse tumor (CA NT) were measured after combined treatments with X-rays and the cytotoxic drug Melphalan. The drug was given as a single dose (10 mg kg-1) with graded single doses of X-rays, either before or after irradiation with an interval of up to 4 days. In the mouse skin, addition of the drug increased the radiation response only slightly. The maximum Enhancement Ratio (ER) measured at a skin reaction of 1.5 (approximately 23 Gy) was 1.07 +/- 0.02 SEM for the schedule MEL 3 days before X-rays. ER's for all schedules tested were similar with a range of 1.00 to 1.07. For the tumor more enhancement was observed; the largest ER's were found when Melphalan was given before rather than after irradiation, with maximum ER's of 2.3 and 2.4 when the drug was given 3 days or 1 day before X-rays. This has been attributed to reoxygenation of hypoxic cells after drug treatment, rendering the tumor more radiosensitive. The range of ER over all schedules was 1.5-2.4. Since ER is greater for the tumor than skin for all schedules, a therapeutic advantage is indicated under these specific experimental conditions of single X-ray and drug doses.
D000818:Animals; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D004890:Erythema / Q000209:etiology; D005533:Foot Dermatoses / Q000209:etiology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000532:radiotherapy*; D011833:Radiation Injuries, Experimental; D011838:Radiation-Sensitizing Agents; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors
D011838:Radiation-Sensitizing Agents; D008558:Melphalan