- Email: [email protected]
Phase I evaluation of R0-07-0582
with N2-N3 multiple cervical nodes from head and neck cancer. The results indicate an 85% (17/20) complete response in the nodes treated with MDF + Hyperthermia, ,in respect to a 47% (6/13) for MDF alone, and a 30% (14/46) for conventional radiotherapy. Other experimental data on the same murine system evidenced a marked synergistic effect of Hyperthermia and Misonidazole (0, 67 mg/g body weight, 30 min. before the first two daily fractions on day 1 and before the 1st fraction in the following days) associated together with MDF. In consideration of these results in mice, suggesting the possibility of a further enhancement of local response, the complete treatment MDF + Hyperthermia rc Misonidazole is being assessed in a selected group of patients.
(8)
COMPARISON OF HYPERBARIC OXYGEN AND MISONIDAZOLE IRRADITION OF MURINE TUMORS
IN FRACTIONATED
Herman D. Suit, M.D.*, Peter Maimonis, M.D. Howard B. Michaels, M.D., and Robert Sedlacek, M.D. Edwin L. Steele Laboratory of Radiation Biology Department of Radiation Medicine Massachusetts General Hospital Harvard Medical School Boston, Massachusetts A comparison of the enhancement ratios for hyperbaric oxygen (30psi) and misonidazole (0.3mg/gm BW given i.p. 30 min. before irradiation) in the treatment of early generation transplants of a spontaneous mamnary carcinoma and a spontaneous squamous cell carcinoma of End points employed were growth the C3Hf/Sed mouse will be discussed. For the treatment, radiation was administered as a delay and TCDSO. Time single dose or in 10 equal radiation doses at daily intervals. courses of tumor tissue level of misonidazole in the unirradiated and in the irradiated tumor were determined for each of the three tumor Tumpr control probabilities are compared for specified levels types. of acute (skin) and of delayed (leg contraction) reactions for the different modalities (control or AIR, 02 30 psi, and misonidazole).
(9)
PHASE I EVALUATION OF RO-07-0582 Richard Johnson, M.D.*, Nasser .!jakissa,M.D. Mike O'Hara, M.D., and Theodore Phillips, M.D. Roswell Park Memorial Institute Buffalo, New York
Twenty-four patients with tumor masses of different histology and sites of origin with widespread metastasis were studied. The age range Toxicity, blood levels and tumor response was between 25 and 80 years. The dose of RO-07-0582 ranged from l-3 gm/mZ. Use of were measured. the medication was discontinued if the development of unacceptable The majority of patients developed clinical side effects occurred. Brisk erythema and moist desnausea that was controlled with Tigan.
30
Less than quamation occurred in less than one third of the patients. one quarter of the patients developed significant peripheral neuropathy ranging from tingling of the fingertips without pain, sensory and motor deficit to severe peripheral neuropathy, hyperesthesia with abnormal Duration of neuropathy in the majority of panerve condution tests. tients was less than two weeks, but in some patients lasted for three Walking difficulty and broad base gait was the most common months. motor sign. Minimal decrease of hearing to total loss was observed in Blurring of vision was seen in one patient. Respiraa few patients. tory difficulty was seen in two patients and one patient developed severe drop of B.P.
(10)
sn_EcTIvE TUMORHEATINGBY SHORTWAVE RADIOFREQUENCY
(RF)
S.P. Auda, M.D.*, H.R. Steinert, M.D., and E.G. Elias, M.D. University of Maryland Department of Surgery Baltimore, Maryland and Surgery Branch, NCI, Bethesda, Maryland Experimental tumor masses were treated with external high frequency dielectric heating to observe any selectivity among tumor mass, subcutaneous tissue and systemic temperatures. Methylcholantrene-induced sarcoma cells were inoculated into the muscles of the posterior thigh of isologous Fisher rats. After 14 days when the size of the tumor mass averaged 1.10 cm3, RF dielectric heating was locally applied to the tumor-bearing area. A fixed frequency of 13.56 MHz was used. The power needed to bring the tumor temperature to 43'C or above ranged from 0.5 to 0.8 watts/cm2. The temperature was gradually increased to 43'C and then maintained at or above that level for 1 hour. Thermocouple probes were inserted directly into the subcutaneous tissue immediately above the tumor and into two distinct areas of the tumor itself. Systemic temperature was monitored via a mercury thermometer inserted into the rectum. Temperature recordings were taken at 5 minute intervals during which time the power was turned off in order to avoid the RF interference and to allow thermal equilibrium between the probe and the tissue. The results indicated that there was a high selective temperature gradient with tumor mass. A highly statistical significance, p 0.002, was found comparing the tumor mass, subcutaneous tissue, and systemic temperatures using Scheffe's test. The systemic temperature was miniIn a group of animals without mally elevated throughout the treatment. tumors, treated in the same fashion, there was no significant difference between the temperatures measured in the subcutaneous tissue and in two different sites in the thigh muscle mass. Samples for histological evaluation were obtained in order to evaluate both tumor and normal tissue damage. At this dosage, we could not observe any tumor regression. The preferential sensitivity of tumor tissue to RF heating has been previously observed clinically and with other experimental models both with this and other frequencies and is certainly an encouragement to further investigate this mode of therapy.
31
(8)
COMPARISON OF HYPERBARIC OXYGEN AND MISONIDAZOLE IRRADITION OF MURINE TUMORS
IN FRACTIONATED
Herman D. Suit, M.D.*, Peter Maimonis, M.D. Howard B. Michaels, M.D., and Robert Sedlacek, M.D. Edwin L. Steele Laboratory of Radiation Biology Department of Radiation Medicine Massachusetts General Hospital Harvard Medical School Boston, Massachusetts A comparison of the enhancement ratios for hyperbaric oxygen (30psi) and misonidazole (0.3mg/gm BW given i.p. 30 min. before irradiation) in the treatment of early generation transplants of a spontaneous mamnary carcinoma and a spontaneous squamous cell carcinoma of End points employed were growth the C3Hf/Sed mouse will be discussed. For the treatment, radiation was administered as a delay and TCDSO. Time single dose or in 10 equal radiation doses at daily intervals. courses of tumor tissue level of misonidazole in the unirradiated and in the irradiated tumor were determined for each of the three tumor Tumpr control probabilities are compared for specified levels types. of acute (skin) and of delayed (leg contraction) reactions for the different modalities (control or AIR, 02 30 psi, and misonidazole).
(9)
PHASE I EVALUATION OF RO-07-0582 Richard Johnson, M.D.*, Nasser .!jakissa,M.D. Mike O'Hara, M.D., and Theodore Phillips, M.D. Roswell Park Memorial Institute Buffalo, New York
Twenty-four patients with tumor masses of different histology and sites of origin with widespread metastasis were studied. The age range Toxicity, blood levels and tumor response was between 25 and 80 years. The dose of RO-07-0582 ranged from l-3 gm/mZ. Use of were measured. the medication was discontinued if the development of unacceptable The majority of patients developed clinical side effects occurred. Brisk erythema and moist desnausea that was controlled with Tigan.
30
Less than quamation occurred in less than one third of the patients. one quarter of the patients developed significant peripheral neuropathy ranging from tingling of the fingertips without pain, sensory and motor deficit to severe peripheral neuropathy, hyperesthesia with abnormal Duration of neuropathy in the majority of panerve condution tests. tients was less than two weeks, but in some patients lasted for three Walking difficulty and broad base gait was the most common months. motor sign. Minimal decrease of hearing to total loss was observed in Blurring of vision was seen in one patient. Respiraa few patients. tory difficulty was seen in two patients and one patient developed severe drop of B.P.
(10)
sn_EcTIvE TUMORHEATINGBY SHORTWAVE RADIOFREQUENCY
(RF)
S.P. Auda, M.D.*, H.R. Steinert, M.D., and E.G. Elias, M.D. University of Maryland Department of Surgery Baltimore, Maryland and Surgery Branch, NCI, Bethesda, Maryland Experimental tumor masses were treated with external high frequency dielectric heating to observe any selectivity among tumor mass, subcutaneous tissue and systemic temperatures. Methylcholantrene-induced sarcoma cells were inoculated into the muscles of the posterior thigh of isologous Fisher rats. After 14 days when the size of the tumor mass averaged 1.10 cm3, RF dielectric heating was locally applied to the tumor-bearing area. A fixed frequency of 13.56 MHz was used. The power needed to bring the tumor temperature to 43'C or above ranged from 0.5 to 0.8 watts/cm2. The temperature was gradually increased to 43'C and then maintained at or above that level for 1 hour. Thermocouple probes were inserted directly into the subcutaneous tissue immediately above the tumor and into two distinct areas of the tumor itself. Systemic temperature was monitored via a mercury thermometer inserted into the rectum. Temperature recordings were taken at 5 minute intervals during which time the power was turned off in order to avoid the RF interference and to allow thermal equilibrium between the probe and the tissue. The results indicated that there was a high selective temperature gradient with tumor mass. A highly statistical significance, p 0.002, was found comparing the tumor mass, subcutaneous tissue, and systemic temperatures using Scheffe's test. The systemic temperature was miniIn a group of animals without mally elevated throughout the treatment. tumors, treated in the same fashion, there was no significant difference between the temperatures measured in the subcutaneous tissue and in two different sites in the thigh muscle mass. Samples for histological evaluation were obtained in order to evaluate both tumor and normal tissue damage. At this dosage, we could not observe any tumor regression. The preferential sensitivity of tumor tissue to RF heating has been previously observed clinically and with other experimental models both with this and other frequencies and is certainly an encouragement to further investigate this mode of therapy.
31