The action of caffeine on X-irradiated HeLa cells. II. Synergistic lethality.
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Caffeine↗
Biomedical subjects
P M Busse
Publications and source records attributed to P M Busse.
Primary site management following induction chemotherapy with cis-platinum, 5-fluorouracil, and leucovorin.
A phase II clinical trial was initiated in 1987 to evaluate a new induction regimen of cis-platinum, 5-fluorouracil, and leucovorin (PFL) for patients with stages III-IV squamous cell carcinoma of the head and neck. Ninety patients were treated and followed for a median duration of 18 months. The median age was 55 and 87% of the patients had stage IV disease. The rates of complete and overall clinical response following three cycles of PFL were 57% and 80%, respectively; the rate of complete response at the primary site was 72%. Eighty-four percent of patients were treated to the primary site with radiation alone (median dose 68 Gy in daily 1.8-Gy fractions) irrespective of the location of the primary site or initial T-stage. The acute tolerance to full-course radiation following PFL was acceptable. The actuarial rate of primary site control for patients treated with radiation was 67% at 36 months. An important prognostic indicator for primary site control was a complete clinical response to induction PFL. For patients who achieved a complete response, radiation or surgery followed by radiation controlled primary site disease equally well at 70%. Patients with a partial response did less well. For these patients, surgery and radiation appeared slightly better than radiation alone.
Actuarial Analysis↗
Evolving role of surgery after induction chemotherapy and primary site radiation in head and neck cancer.
Chemotherapy, as preliminary treatment before surgery and/or radiation for advanced squamous cell carcinoma of the head and neck, is no longer novel. In prospective trials to date, however, multiple agent induction chemotherapy has yet to demonstrate the initial presumptive promise of improved rates of cure. As an alternate goal, there has emerged a renewed attentiveness toward limiting treatment morbidity, several strategies for which may be considered. Extirpative, often radical, surgery on the primary site of disease usually represents the most significant threat to life quality. Various ways of limiting surgical morbidity will be considered by way of introduction. The trends of head and neck cancer treatment over the decades, leading into the era of induction chemotherapy and refined radiation techniques, will be described. At the combined Dana-Farber/New England Deaconess Head and Neck Oncology Clinic, an experience with over 300 patients receiving induction chemotherapy for advanced head and neck cancer has been analyzed with an emphasis on the postulate of lessening the extent of surgery in appropriately selected patients. In a comparison between trials initiated in 1980 and 1987, improved complete response rates from 26 to 57% were documented. Survival rates were identical, but the use of planned primary site ablative surgery was decreased from 47 to 14%. While some increase in local failure has been noted in patients treated by primary site radiation alone, surgical salvage appeared to be more effective. The implication of these trends for patterns of failure and surgical salvage and data concerning the need for neck dissection in this group of patients will be briefly summarized. Other trials addressing organ-preservation strategies will also be referenced and the dichotomy between survival-based studies and morbidity-limiting studies illustrated. Independent trends in radiation technique as a potential substitute for traditional surgical practice will be reviewed.
Antineoplastic Agents↗
Effect of combined modality therapy on the surgical management of locally advanced rectal carcinoma.
The treatment of locally advanced rectal carcinoma is one of the more complicated problems in the management of colorectal carcinoma. More than any other site successful treatment requires a multimodality approach as surgery alone is frequently insufficient to completely eradicate all disease. This review focuses primarily on the management of patients who present without prior treatment and discusses the role of preoperative radiation therapy as well as intraoperative radiation therapy. Although much less gratifying, patients who present after failing previous therapy may also benefit from an aggressive multimodality approach.
Carcinoma↗
Intraoperative radiation therapy for carcinoma of the gallbladder.
The recognition of a high incidence of local failure following surgical management of adenocarcinoma of the gallbladder has led to the use of adjuvant radiation therapy. In order to deliver higher doses to the gallbladder bed, intraoperative radiation therapy (IORT) has been used both with and without external beam radiation. The experience to date is reviewed. Ten patients have been treated, all of whom had either gross residual or unresected disease. The median survival for the group was approximately 1 year. There were no long-term survivors. The IORT did not contribute to the overall morbidity. Because of the limited number of patients and the advanced nature of the disease, the role of IORT in the management of gallbladder carcinoma has yet to be determined. The utility of this modality will most likely reside in the treatment of minimal residual disease at the time of cholecystectomy rather than in the palliative treatment of unresectable tumors.
Adenocarcinoma↗
Pharamacokinetic modeling for boronophenylalanine-fructose mediated neutron capture therapy: 10B concentration predictions and dosimetric consequences.
A two-compartment open model has been developed for predicting 10B concentrations in blood following intravenous infusion of the L-p-boronophenylalanine-fructose complex in humans and derived from pharmacokinetic studies of 24 patients in Phase I clinical trials of boron neutron capture therapy. The 10B concentration profile in blood exhibits a characteristic rise during the infusion to a peak of approximately 32 microg/g (for infusion of 350 mg/kg over 90 min) followed by a biexponential disposition profile with harmonic mean half-lives of 0.32 +/- 0.08 and 8.2 +/- 2.7 h, most likely due to redistribution and primarily renal elimination, respectively. The mean model rate constants k12, k21, and k10 are (mean +/- SD) 0.0227 +/- 0.0064 min(-1), 0.0099 +/- 0.0027 min(-1), 0.0052 +/- 0.0016 min(-1), respectively, and the central compartment volume of distribution V1 is 0.235 +/- 0.042 L/kg. In anticipation of the initiation of clinical trials using an intense neutron beam with concomitantly short irradiations, the ability of this model to predict, in advance, the average blood 10B concentration during brief irradiations was simulated in a retrospective analysis of the pharmacokinetic data from these patients. The prediction error for blood boron concentration and its effect on simulated dose delivered for each irradiation field are reported for three different prediction strategies. In this simulation, error in delivered dose (or, equivalently, neutron fluence) for a given single irradiation field resulting from error in predicted blood 10B concentration was limited to less than 10%. In practice, lower dose errors can be achieved by delivering each field in two fractions (on two separate days) and by adjusting the second fraction's dose to offset error in the first.
Boron↗