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Biomedical subjects

J Stetz

Publications and source records attributed to J Stetz.

28 records · Page 2Linked to original sources
PubMed1987

Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study.

In patients who have locally advanced and inoperable head and neck cancer, the achievement of initial local control (complete response) of the disease with initial definitive treatment with radiotherapy (RT) with or without chemotherapy, is an important prognostic factor for overall survival. Cisplatin 100 mg/M2-intravenously (IV) with hydration and mannitol diuresis was given every 3 weeks for three doses concurrently with definitive radiotherapy (followed by salvage surgery [if possible] for persistent disease) was activated by the Radiation Therapy Oncology Group (RTOG) in 1981. One hundred thirty-four patients were initially registered and 124 were eligible and analyzed for this report. Eighty-two percent of the patients had Stage IV disease and greater than 50% of the primary sites were in oropharynx (39%), nasopharynx (22%), and oral cavity (18%). Eighty-seven percent of the patients are known to have finished the planned RT greater than 6450 cGy and 60% received three courses of cisplatin. Overall, 60% finished the planned combined treatment. Complete response to initial treatment occurred in 69% and an additional one patient (1%) was rendered disease-free after radical node dissection. Severe toxicities were as follows: leukopenia, 11%; anemia, 8%; nausea and vomiting, 6%; stomatitis, 31%; and renal, 6%. One toxic death occurred when a nephrotoxic antibiotic was administered at the same time. All patients were evaluated for total disease and survival regardless of compliance to the treatment or the cause of death. At 1 year, an estimated 51% of the patients had their disease totally controlled and an estimated 66% were alive. Incidence of initial complete response by various patient characteristics also were analyzed. The authors concluded that the combination of cisplatin and radiotherapy is an effective and safe treatment in patients with advanced head and neck cancer and needs to be tested against radiotherapy alone.

Adult↗
PubMed1987

Failure of misonidazole-sensitized radiotherapy to impact upon outcome among stage III-IV squamous cancers of the head and neck.

As part of the RTOG research effort in the treatment of advanced, inoperable squamous cancer of the head and neck region, the hypoxic cell sensitizer, misonidazole, was selected for investigation as an adjuvant to definitive irradiation. Based upon a pilot experience (78-02) showing a 67% complete response rate among 36 AJC Stage III-IV patients receiving full-dose irradiation and 6 weekly p.o. doses of misonidazole, a phase III trial was carried out from '79-'83. Three hundred and six patients were entered, 42% of whom had oropharyngeal primaries and with 78% of all cases representing T3 or T4 (inoperable) lesions. Only 16% of the entire series presented with N0 necks. Fractionation was altered among the misonidazole-receiving patients, in contrast to "standard" 5 treatments per week among "control" patients, such that 2 separate treatments were given on each day of p.o. misonidazole administration (2.0 gm/m2/wk X 6 doses, 2.5 Gy in a.m., 2.1 Gy in p.m.). Total tumor doses were identical among the two treatment arms except that a limitation of 40.0 Gy to spinal cord was specified for sensitized radiotherapy vs. 45.0 Gy for "control" patients. Primary tumor clearance was observed to be 55-60%, with minor variations according to tumor stage and site. The local regional control rate among radiotherapy-alone patients was 26% at 2 years compared to 22% (2 years) within the misonidazole-receiving group. Analysis of survival revealed no advantage to the sensitized patients, with 55 +/- 2% surviving 1 year and 22 +/- 1% living 3 years following treatment in both treatment categories. Distant metastases as first site of failure (12-13%) and the local failure among initial complete responders (46%) showed no advantage to the misonidazole group. Although a misonidazole dosage of 2.0 gm/m2/wk X 6 (12 gm/m2 total) is well tolerated, no clinical benefit was demonstrated in this randomized trial. Other nitroimidazole analogs (e.g. SR-2508) are now being investigated.

Aged↗
PubMed1987

Hyperfractionated photon radiation therapy in the treatment of advanced squamous cell carcinoma of the oral cavity, pharynx, larynx, and sinuses, using radiation therapy as the only planned modality: (preliminary report) by the Radiation Therapy Oncology Group (RTOG).

From August 1979 to June 1983, the RTOG conducted a prospective Phase III study that compared a standard schedule with five fractions per week of 180 to 200 cGy per day to a total dose of 6600-7380 cGy, with a hyperfractionation regimen consisting of two fractions of 120 cGy per day, separated by a rest period of 3 to 6 hours for a total of 6000 cGy. A total of 210 patients were entered, of which 187 are analyzed. Complete initial tumor clearance in the head and neck was achieved by radiotherapy in 61% of the patients assigned to the standard schedules and in 59% of those assigned to the continuous hyperfractionation schedule; surgical salvage contributed towards achieving complete response in 5% and 7% of patients, respectively. The Kaplan-Meier estimates for loco-regional control of tumor at 1 and 2 years was 39% and 29% for the standard schedules, and 43% and 30% for the hyperfractionation schedule. The endpoints examined to evaluate therapeutic effects do not indicate that the stated hyperfractionation schedule is different than the standard RTOG treatment schedule for head and neck cancer. Acute normal tissue reactions appear to be more severe with the hyperfractionation schedule but the incidence of late reactions is similar in both groups. There is a tendency toward more severe acute reactions when the interval between the two fractions per day is 4.5 hrs or less in comparison to intervals longer than 4.5 hrs.

Aged↗
PubMed1987

Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG phase I/II study.

Between October 1979 and June 1982 forty-six patients were entered on a non-randomized Phase I-II protocol for the evaluation of Misonidazole combined with high dose per fraction radiation for the treatment of advanced pelvic malignancies. Pelvic radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a total of three treatments. Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2). The distribution of histology consisted of 20 gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients completing the three treatments; there were 6 complete responses (14% CR), 10 partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable. One patient remains NED 5.5 years following radiation. Toxicity directly related to Misonidazole was minimal and consisted primarily of transcient Grade 1, 2 peripheral neuropathy (20% Grade 1, 4% Grade 2) and Grade 2 ototoxicity (4%). Radiation toxicity was significant for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal (GI) toxicities. Kaplan-Meier plot of GI toxicity showed a progressive increase in incidence with time for projected rate of 49% Grade 3, 4 by 12-month. GI toxicity (Grade 3, 4) was also related to tumor response. The complication rate was 80% (4/6) for CR, 30% (3/10) for PR and 26% (5/19) for NR or progression. Because of the GI complication rate, this protocol for palliation of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over 2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3 courses.

Combined Modality Therapy↗
PubMed1984

Treatment-related morbidity in phase III RTOG studies of extended-field irradiation for carcinoma of the prostate.

The incidence, severity, time of onset, and clinical course of complications of treatment have been reviewed in the RTOG studies of extended field irradiation in carcinoma of the prostate. A total of 526 patients, entered between 1976 and 1980 and followed for a minimum of 18 months, comprised the study population. In most instances of treatment-related morbidity, the symptoms were recorded during the first several months to 1 year following completion of treatment. Late occurrences, however, were not uncommon in certain types of radiation-produced injuries, such as proctitis, hematuria, and urethral strictures. Resolution of symptoms has been observed in a large proportion of patients including those with late occurrences of treatment-related morbidity, although the probability and the pattern of resolution differed considerably from one type of morbidity to another. Symptoms of cystitis are more likely to abate than those of proctitis. In patients who develop symptoms of proctitis the probability of persistence of symptoms beyond the second year following occurrence has been estimated at 20%-30%. Hematuria and symptoms secondary to urethral strictures seem to be even more likely to recur or persist, while genital and leg edema remain chronic in the majority of patients.

Adenocarcinoma↗
PubMed1984

Is misonidazole neurotoxicity altered by the use of phenytoin and/or dexamethasone in RTOG 79-18 and RTOG 79-16?

An analysis of Misonidazole (MISO) neurotoxicity in RTOG 79-16 and RTOG 79-18 was undertaken to evaluate the incidence of neurotoxicity relative to dexamethasone dose and phenytoin use. MISO was administered as follows: 79-16 arm A, 1 gm/m2 5 days a week for a total of 10 gm/m2 in 2 weeks; 79-16 arm B, 2 gm/m2 twice weekly for a total of 12 gm/m2 in 3 weeks; and 79-18, 2.5 gm/m2 once a week for a total of 15 gm/m2 in 6 weeks. Practically all patients were on dexamethasone, and 240 out of 550 were on phenytoin for seizures. CNS toxicity and ototoxicity rates were no different between treatment groups with overall rates of 2.7 and 1.1%, respectively. Peripheral neuropathy (PN) was 5.1% in 79-16 arm A, 5.9% in 79-16 arm B, and 8.7% in 79-18. Phenytoin did not significantly alter CNS and PN toxicity rates. All ototoxicities occurred in patients not on phenytoin. There was no correlation between dexamethasone dose and incidence of neurotoxicity within each study. However, the incidence of (PN) for the combined studies was 6.4% (35/550) which is lower than 18.9% (85/449) for non-brain Phase III protocols where patients are rarely, if ever, on dexamethasone or other corticosteroids. Four hour and 24 hour plasma MISO levels, and 24 hour/4 hour MISO ratios did not correlate with toxicity.

Brain Neoplasms↗
PubMed1983

Preliminary report on phase III RTOG studies of extended-field irradiation in carcinoma of the prostate.

The radiation therapy oncology group (RTOG) has conducted two studies testing the value of extended-versus limited-fields in carcinoma of the prostate. RTOG protocol 75-06 tests the value of paraaortic irradiation in patients with locally advanced tumors limited to the pelvis. RTOG protocol 77-06 tests the value of pelvic irradiation in patients with tumors limited to the prostate. Two hundred sixty-eight evaluable patients have been entered on RTOG 75-06, and 219 on RTOG 77-06 prior to 1981. This is a preliminary report on treatment-related morbidity in patients followed for a minimum of 1 year. Treatment-related morbidity has been classified according to a five-grade severity classification schema and correlated with the protocol option assignment in order to determine whether the use of extended fields had an effect on the incidence of side effects. Thirty-one percent of 268 patients on RTOG 75-06 and 34% of 219 patients on RTOG 77-06 had some form of treatment side effects. The majority (over 80%) of these were mild (grade 1 and 2) and by definition did not interfere with the patients' performance (life style). Only three patients on RTOG 75-06 and one on RTOG 77-06 had grade 4 complications (by definition requiring a surgical intervention). No fatal (grade 5) complications have been recorded so far. The use of paraaortic fields in RTOG 75-06 and pelvic fields in RTOG 77-06 have not resulted in a significant increase of GI or GU morbidity at this time. The only statistically significant trend was the incidence of postirradiation genital and lower extremity edema which strongly correlated with the extent of staging lymphadenectomy.

Aged↗
PubMed1981

Radiation Therapy Oncology Group clinical trials with misonidazole.

This paper presents a review of the progressive clinical trials of the hypoxic cell radiosensitizer, misonidazole, in the Radiation Therapy Oncology Group (RTOG). Presentation is made of all the schemas of the recently completed and currently active RTOG Phase II and Phase III studies. Detailed information is provided on the clinical toxicity of the Phase 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 better than previous radiation experience. A series of eight Phase III trials are currently underway or proposed in the RTOG and the results of these are pending. An additional Phase III malignant glioma trial in the Brain tumor Study Group is described.

Brain Neoplasms↗
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↗