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Biomedical subjects

T L Phillips

Publications and source records attributed to T L Phillips.

At least 181 records · Page 10Linked to original sources
PubMed1981

Treatment of carcinoma of the vocal cord. A review of 20 years experience.

At the University of California, San Francisco, 323 patients were treated for carcinoma of the vocal cord between January 1956 and December 1975. Patients with early T1 or T2 lesions were treated with radiotherapy or conservative surgery. Patients with T3 or T4 lesions were treated with total laryngectomy, radiation alone, or combined therapy. Of the 247 patients treated with definitive radiotherapy, initial control of the primary lesion was achieved in 100% of T1S, 80% of T1, 52% of T2, and 50% of T3 and T4 lesions. Surgical salvage of radiation failures was 86%, giving ultimate control rates in this group of 100% for T1S, 97% for T1, 91% for T2 and 64% for T3 and T4. Involvement of the anterior commissure did not significantly affect local control or survival rates of the irradiated patients. Voice quality was satisfactory in 95% of controlled patients. Surgery alone was used as the primary treatment modality in 63 patients, with ultimate local control achieved in 75% of T1S, 83% of T1, 85% of T2, 81% of T3 and T4 lesions. Planned combined therapy was successful in 9/13 patients in whom it was used. The overall 3 and 5 year actuarial survival rates were 84% and 77% respectively corresponding determinate survival rates were 90% and 86%.

Aged↗
PubMed1981

Differential protection against cytotoxic chemotherapeutic effects on bone marrow CFUs by Wr-2721.

This paper reports on the ability of the radioprotector WR-2721 to protect bone marrow colony forming units from the cell kill of various cytotoxic chemotherapy agents including nitrogen mustard, cyclophosphamide, BCNU, cis-platinum, and 5-fluorouracil. The dose-modifying factors seen with these compounds ranged from 1.5 to 4.6. Protection by WR-2721 seems to be selective for the bone marrow endpoint, in that similar protection against EMT6/SF tumor cell kill was not seen with the same combination of the cytotoxic chemotherapy agents and WR-2721 as measured by regrowth delay. The implications of these data are discussed in the paper.

Amifostine↗
PubMed1981

Stereotactic interstitial irradiation for the treatment of brain tumors.

Eighteen patients harboring untreated, inaccessible, slow-growing tumors or recurrent malignant primary or metastatic brain tumors were treated by the stereotactic implantation of permanent or removable radioactive seeds (192Ir, 198Au, 125I). Seed strength was selected to deliver 10,000-12,000 rad to the tumor's periphery for 192Ir, 9000-12,000 rad for 125I, and 4000-7500 rad for 198Au. Three of six patients implanted with 192Ir seeds had objective responses for 2, 8, and 12 months, and a fourth stabilized for 20 months. Five of 9 patients treated with 198Au were evaluable, three of whom responded for 3, 5, and 20 months. Two patients who received 125I have been evaluated to date and are early failures. Two patients who received 125I have been evaluated to date and are early failures. Because of its higher dose rate 198Au is superior for the faster-growing malignant tumors; but because 125I is easier to shield, 125I seeds with greater activity are being developed for evaluation.

Brachytherapy↗
PubMed1981

Clinical trials of misonidazole in the United States.

This paper presents a review of the progressive clinical trials of the hypoxic cell radiosensitizer, misonidazole, in the United States. Presentation is made of all of the schemata of the recently completed and currently active Radiation Therapy Oncology Group (RTOG) phase II and phase III studies. Detailed information is presented on the clinical toxicity of the phase I and II trials, specifically regarding neurotoxicity. With limitations in drug total dose, a variety of dose schedules have proven to be tolerable, with a moderate incidence of nausea and vomiting and mild peripheral neuropathy, and a low incidence of more severe peripheral neuropathy or central neuropathy. No other organ toxicity has been seen, specifically no liver, renal, or bone marrow toxicities. The clinical pharmacologic monitoring of misonidazole blood levels has been satisfactory with good correlation between the group-wide (phase II) UV values and the HPLC values from the phase I study. The patient accrual of the trials has been rapidly increasing and an early analysis suggests efficacy which is at least comparable to previous radiation experience. A series of the five phase III trials are currently underway in the RTOG and the results of these are pending. An additional malignant glioma trial in the Brain Tumor Study Group is described.

Drug Evaluation↗
PubMed1980

Current status of clinical particle radiotherapy at Lawrence Berkeley Laboratory.

Clinical experience with charged particle irradiation of human cancers has been underway at the University of California Lawrence Berkeley Laboratory. Over 150 patients have been irradiated with heavy charged particle beams including helium, carbon, neon, and argon ions. Pilot studies have included such tumor sites as glioma of the brain, carcinoma of the esophagus, carcinoma of the pancreas, carcinoma of the stomach, ocular melanoma, and carcinoma of the uterine cervix. Prospective studies are planned to investigate the improved dose localization potential (helium) and the enhanced biologic and physical dose potential (carbon, neon) in a controlled trial against the best available megavoltage irradiation techniques.

Argon↗
PubMed1980

Development of a computed tomographic scanner for radiation therapy treatment planning.

The authors describe a low-cost CT scanner integrated with a radiotherapy simulator and designed for treatment planning. The standard rotational gantry and x-ray tube of the simulator are used with a multiwire xenon lonization chamber and simple current-proportional readout system to measure patient attenuation, avoiding problems associated with diagnostic CT scanners in treatment planning. Although design constraints limit performance, software compensation techniques have reduced artifacts and given satisfactory images.

Evaluation Studies as Topic↗
PubMed1980

Hypoxic cell radiosensitizers in the treatment of malignant brain tumors.

Radiation therapy provides the most effective adjuvant treatment for patients with malignant brain tumors, but brain intolerance to potentially curative doses of radiation is limiting. Solid tumors are thought to contain a substantial population of cells that are hypoxic; because much of the cell kill caused by ionizing radiation is the result of an oxygen-dependent, free radical-mediated attack on deoxyribonucleic acid, hypoxic tumor cells are known to be radioresistant and are therefore a barrier to cure. With the hope of improving the therapeutic ratio of brain tumor radiation therapy, hypoxic cell radiosensitizers are being evaluated. Two nitroimidazoles, metronidazole and misonidazole, have received the most attention. These compounds are thought to mimic oxygen by "fixing" the free free radical-induced damage caused by radiation in tumor cells. Clinical trials ae providing considerable information about the pharmacokinetics and toxicities of these agents. The preliminary results obtained in clinical trials with brain tumor patients are somewhat discouraging; drug toxicity limits the number of radiation treatments with which a sensitizer may be given. The results of ongoing clinical trials with metronidazole and misonidazole and the identificiation of new, less toxic hypoxic cells sensitizers may improve the potential for this modality of therapy.

Animals↗
PubMed1980

Interstitial brachytherapy of primary brain tumors. Preliminary report.

Ten patients harboring inaccessible, slow-growing or recurrent malignant primary brain tumors were treated by the stereotaxic implantation of a radionuclide seed -- iridium-192 (192Ir) or gold-198 (198Au) -- either permanent or removable. The strength for 192Ir seeds was selected to deliver 10,000 to 12,000 rads to the periphery of the tumor, and that for 198Au seeds to deliver 4000 to 7500 rads. Three of the six patients treated with 192Ir showed objective responses lasting 8, 11, and 12 months, respectively; and one patient's disease stabilized for 18 months. Three of the four treated with 198Au showed responses lasting 5 months, 6 months, and 2 years, respectively. Because of the higher dose-rate attainable with 198Au, removable implants of this material are more effective against the faster-growing malignant tumors. Another radionuclide, iodine-125 (125I), is now being tested against brain tumors. The radioactivity of 125I is high; but because its gamma emission is less energetic by a factor of 10 than that of 198Au or 192Ir, its radiation field is concentrated within a radius of 2.5 cm or less. This low-energy gamma emission also makes it easier to protect medical personnel and the patients' families against the nuclide when 125I is used.

Adult↗
PubMed1980

Therapy of hepatocellular cancer with combined intrahepatic arterial chemotherapy and whole liver irradiation.

Hepatocellular cancer provides an ideal model for studying combined modality chemotherapy and radiation interactions. We have treated 20 evaluable patients. All patients received intrahepatic arterial (IA) 5 FU (10 mg/kg/d continuous infusion times 5 minus 9 d) + Adriamycin (3-5 mg/m(2)/d bolus times 5 minus 7 d), and 1,500 and 2,100 rads whole liver radiation (300 rads/day). Additionally, 3 patients have received IA Mitomycin C (8 mg/m(2)). After this "induction" therapy patients usually received IV Adriamycin + 5FU +/- Mitomycin monthly. Objective regressions occurred in 9/20 (45%) and another 9/20 (45%) and stable disease. Median duration of response is 5+ months (range 1+ to 8 months). Improvement in liver function tests occurred in 11/19, and local symptomatic relief in 12/15. Median WBC nadir = 4,000; platelet nadir = 115,000. Mild anorexia, fever, and nausea were frequent, but no radiation hepatitis has been detected. This program seems to result in significant clinical benefit (subjective and objective) in this refractory neoplasm.

Adult↗
PubMed1980

Rationale for initial clinical trials and future development of radioprotectors.

Over the past two decades a number of chemical radioprotectors have been developed which, although toxic, appear to be usable in clinically relevant doses. Because of differences in blood flow, radiochemical action in hypoxic cells, and active concentration in certain normal tissues, these compounds exhibit differential protection of normal tissue versus tumor. The best, currently available protector, WR-2721, is active in skin, intestine, marrow, mucosa, and salivary glands with lesser activity in kidney and lung and none in brain. Clinical trials have been designed in the Radiation Therapy Oncology Group based on this knowledge. Phase I studies involve patients requiring palliative radiotherapy for tumors located in or adjacent to tissues which are known to be protected. These studies use excalating doses of WR-2721, starting at 50 mg/m2 and will determine the maximum tolerated dose of drug, first as single doses and then as 1X, 3X, and 5X weekly for 3 and 6 weeks. Concomitant radiotherapy is given and normal tissue response at conventionl doses observed. Phase II studies will be site specific based on phase I results and doses. They will be radiation dose ranging studies designed to determine the maximum acceptable radiation dose at each site with WR-2721 protection. These new, higher doses will then be compared to conventional radiotherapy without protector, seeking increased tumor control in phase III studies. WR-2721 is not the ideal sensitizer since it does not protect all normal tissues. It is particularly important to develop compounds which can protect the brain, spinal cord, and lung. A large effort in new drug development will be justified if an improved therapeutic ratio is observed with WR-2721.

Amifostine↗