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Biomedical subjects

K Mattson

Publications and source records attributed to K Mattson.

At least 127 records · Page 7Linked to original sources
PubMed1988

Inoperable non-small cell lung cancer: radiation with or without chemotherapy.

We report a randomized multicentre study of split-course radiotherapy (RT), with or without combination chemotherapy (CT), in 238 patients with inoperable non-small cell lung cancer (NSCLC), previously untreated, confined to one hemithorax and the mediastinal nodes. In both treatment groups RT consisted of 55 Gy in 20 F given over 7 weeks with a 3-week rest interval. CT consisted of the 3-drug regimen CAP: C = cyclophosphamide 400 mg/m2, A = adriamycin 40 mg/m2, P = cisplatin 40 mg/m2; 2 cycles of CAP given before RT, one during the rest interval and six after RT. Seventy per cent in the RT arm and 67% in the RT-CT arm had epidermoid carcinoma. No significant difference was apparent between the RT and the RT-CT arms with respect to objective response rates (CR + PR) (44 and 49%, respectively), median duration of response (278 and 320 days), local failure (31 and 20%), distant progression (23 and 20%) or median survival (311 and 322 days). The survival figures showed an almost significant (P = 0.05) therapeutic advantage of the combined regimen with stage IIIM0 disease. Progressive disease was the cause of death in 92% and 88%. We conclude that chemotherapy did not contribute significantly to either local control or survival as compared to radiotherapy alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Effect of interferon-gamma on biogenic amine metabolism, electroencephalographic recordings, and transient potentials.

For assessment of the underlying central mechanisms of interferon (IFN), measurements have been made of the neurotoxicity, cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) concentrations, along with electroencephalographic (EEG) recordings and visual evoked potentials (VEP) during recombinant IFN-gamma therapy. Interferon-gamma was administered intravenously to 14 patients with non-small-cell lung cancer as 2 mg/m2 (48 X 10(6) IU/m2) three times weekly with 4 h infusion for 12 weeks. The cerebrospinal fluid (CSF) samples were taken by means of lumbar puncture prior to treatment and during the end of the second week of IFN-gamma infusions. During the course of treatment, CSF 5-HIAA diminished from 129.6 +/- 10.9 to 84.5 +/- 10.4 nmol/L (p less than 0.001), while no significant changes were observed in HVA, EEG, and VEPs. These results suggest that IFN-gamma has an effect on the central serotonergic neurotransmission.

Biogenic Amines↗
PubMed1988

Behavioral assessment of patients treated with alpha-interferon.

To document behavioral effects of interferon (IFN) with daily consecutive assessments we developed an easily administered procedure for bedside testing. It included assessment of mental control and affective behavior, and a self-assessment questionnaire. The method was evaluated in 9 lung cancer patients before and during the treatment with alpha-IFN and the results were supplemented with those obtained by a neuropsychological test battery of one of the patients. The latter tests covered memory, visuoperceptual, visuoconstructional, speech, language, intellectual and psychomotor functions, reading, writing, and calculation. The bedside method was capable of revealing the essential effects of IFN on human behavior, i.e. irritability, slowing of behavior, dyscoordination, and motor perseveration. Consequently, the bedside testing method is recommended for frequently repeated clinical assessments of aberrant behavior of patients treated with IFN, while neuropsychological test batteries serve better for testing situations requiring more detailed and quantified data of localization value.

Aged↗
PubMed1988

Trimetrexate and cyclophosphamide for metastatic inoperable nonsmall cell lung cancer.

To determine the maximum tolerated dose (MTD) of trimetrexate glucuronate in combination with cyclophosphamide in patients with metastatic or inoperable nonsmall cell lung cancer (NSCLC), trimetrexate in dosages ranging from 3 to 13.5 mg/m2/day was administered intravenously (IV) to 27 patients for 5 days in combination with cyclophosphamide, 600 mg/m2, on day 1. Patients received between one and six courses of treatment at 3 week intervals, 69 treatment courses in all. Hematological toxicity was mainly mild anemia (81%), leukopenia (67%), and thrombocytopenia (52%). Nonhematological toxicity included nausea and vomiting (67%), mucositis (30%), and urticaria or rash (22%). The incidences of leukopenia and mucositis were dose related. The MTD of trimetrexate in combination with cyclophosphamide was 7.5 mg/m2/day. The dosage chosen for the Phase 2 study, based only on the hematological dose limiting toxicity, was 10.5 mg/m2/day. Of 31 patients with previously untreated metastatic or inoperable NSCLC who have entered in the Phase 2 study, 22 are evaluable for clinical efficacy (World Health Organization criteria, 1979). Treatment was discontinued in four patients because of toxicity. One patient refused further therapy. Four patients are too early to evaluate. Five patients had confirmed partial responses (23%), 12 patients achieved stable disease (54%), and five patients had progressive disease. Results suggest that trimetrexate 10.5 mg/m2/day in combination with cyclophosphamide is active against previously untreated NSCLC. Dose limiting toxicity was mucositis and myelosuppression. An 11 item linear analogue scale assessing quality of life during treatment indicated this combination was well accepted by patients and did not compromise quality of life. The Phase 2 study is continuing.

Adult↗
PubMed1988

Dementia-like, largely reversible syndrome after cranial irradiation and prolonged interferon treatment.

An elderly man with small cell lung cancer developed a largely reversible, dementia-like syndrome after cranial irradiation and prolonged treatment with interferon (IFN). The development of the symptoms started 2 months after cranial irradiation following more than 2 years of IFN treatment. The behavioral impairment did not suggest any specific brain localization. The dementia-like behaviour may be due to a combined effect of irradiation and IFN.

Aged↗
PubMed1987

Enhancement of radiation effects by alpha interferon in the treatment of small cell carcinoma of the lung.

The effects on lung tissue and tumor of natural human alpha interferon (IFN) and radiotherapy were investigated in a multimodality treatment program for selected patients with small cell carcinoma of the lung (SCLC). Interferon was given first as a single agent, then concomitantly with radiotherapy to 12 previously untreated patients with limited disease. At disease progression outside the chest, interferon was discontinued and combination chemotherapy was initiated. In the first series, 7 patients received a high interferon induction dose (800 X 10(6) IU i.v. over 5 days) followed by low-dose maintenance therapy (6 X 10(6) IU i.m. TIW), median total dose 1380 X 10(6) IU (range 794-2074). At local progression, split-course radiotherapy, 55 Gy/20 F/7 wk, was added to interferon therapy. In the second series, 5 patients received low-dose interferon from the start (6 X 10(6) IU i.m. daily) combined with twice-a-day fractionated radiotherapy 44 Gy/40 F/4 wk. Median total dose of interferon in this series was 698 X 10(6) IU (range 354-828). Tumor response and normal tissue reactions were evaluated by monthly chest X rays, 3-monthly CT scans, restaging bronchoscopies and by serial respiratory function tests. Autopsy specimens from both lungs within and outside the radiation field were systematically evaluated when available. After the completion of radiotherapy, there were 4/7 CR in the high-dose IFN group compared to 3/5 CR in the low-dose IFN group. Rapid shrinkage of huge tumor masses was observed. At 2 months post radiotherapy radiological grade III fibrosis occurred in 4/7 patients in the high-dose and 1/5 patients in the low-dose group. Lung function studies showed a significant decrease in diffusing capacity and in lung volumes. Seven patients died within 12 months from start of interferon treatment, one of them from treatment complication. At autopsy the tumor area was in most cases replaced by severe fibrosis. Outside the radiation field lung fibrosis was mild. Our results suggest enhancement of radiation effect by interferon with a possible dose and/or schedule dependence of interferon and radiotherapy and call for more clinical studies of IFN and radiotherapy in combination.

Carcinoma, Small Cell↗
PubMed1987

Antiemetic efficacy of nabilone and dexamethasone: a randomized study of patients with lung cancer receiving chemotherapy.

In a previous study on the antiemetic effect of nabilone (N) in patients with lung cancer receiving chemotherapy (CT), we found that N was only moderately effective and that its side effects limited its use, especially in elderly outpatients. We, therefore, performed a new study of N in combination with dexamethasone (DXM), a potent antiemetic in itself, to evaluate whether the addition of DXM to N would improve the antiemetic effect and/or reduce the side effects. Forty patients with lung cancer were enrolled in the study. A randomized, third-party-blinded, crossover design was used. Study drugs were given during two consecutive, identical CT cycles. N was given at a fixed dosage regimen of 2 mg b.i.d. The initial dose was administered the evening before CT, the second dose at 0.5 h before CT, and the third dose in the evening 12 h after CT. DXM, 8 mg, or placebo was given orally with the first dose of N. The subsequent doses (either 10 mg DXM or saline) were given intravenously 0.5 h before CT and at 2 and 6 h after the start of CT. The CT regimens given included the following drugs in various combinations: cisplatin, cyclophosphamide, adriamycin, etoposide (VP-16), vincristine, and vindesine. The combination of N and DXM was significantly superior to N alone in the reduction of vomiting episodes, both in subgroups of patients receiving cisplatin and in those receiving other CT combinations. There was no statistically significant difference between the treatments with regard to the patients' assessments of the severity of nausea or effects on appetite. Approximately half the patients (63% with N plus DXM versus 47% with N) reported no side effects. The frequency and severity of central nervous system adverse reactions, mainly vertigo, were similar in both treatment groups. The fall in blood pressure was significantly greater after N alone. Two thirds of the patients preferred N plus DXM. Thus, the addition of DXM to N enhanced the therapeutic yield of N, and we recommend DXM as an adjunct to N, when the use of steroids is not contraindicated. The optimal dose and schedule of DXM was not investigated in our study; a higher dose of DXM might increase the clinical benefit of the drug combination tested.

Antiemetics↗
PubMed1987

Vincristine-cyclophosphamide, the classical two-drug regimen for small-cell lung cancer, evaluated in a randomized study with vindesine.

We performed a randomized study from February 1979 to August 1981 in patients with small-cell lung cancer (SCLC) with the aim of defining the potential advantages of replacing vincristine (VCR) with vindesine (VDS), at that time a new semisynthetic vinca alcaloid, in the classical two-drug combination cyclophosphamide (CTX)-VCR. A total of 116 previously untreated patients were admitted to the study. Of 104 patients evaluable for response, 49 had limited disease and 55 extensive disease. Patients received 10 mg/kg CTX i.v. on days 1-4 and either 1 mg VCR i.v. or 2 mg/m2 VDS i.v. on days 1 and 4, and repeatedly every 4 weeks for 12 courses. In addition, the patients with limited disease received split-course radiotherapy (30 Gy/10 F, 3 or 5 weeks rest, 25 Gy/10 F, total treatment time 7 or 9 weeks) to the primary tumor, the mediastinum, and the supraclavicular areas between the second and third cycles of chemotherapy. The response rate to the first two chemotherapy cycles was 47% (4 complete response [CR] and 22 partial response [PR]) to CTX-VCR and 47% (4 CR and 19 PR) to CTX-VDS. Subsequent to radiotherapy the response rate increased to 93% for CTX-VCR and 100% to CTX-VDS, respectively, in the patients with limited disease. Local recurrence and/or progression occurred in 49% of limited disease responders and in 96% of extensive disease responders. In responders with limited disease, the first site of relapse was loco-regional in 25% for the VDS group as opposed to 15% in VCR group. In the patients with extensive disease, the corresponding figures were 62% for the VDS and 50% for the VCR group. Median duration of remission in all patients treated with CTX-VCR was 132 days compared to 203 days in the CTX-VDS group (not significant, NS). Median survival was 338 days for CTX-VCR vs. 342 for CTX-VDS in patients with limited disease, and 214 days for CTX-VCR vs. 312 days for CTX-VDS in extensive disease (NS). One-year survival figures were 47% for CTX-VDS and 35% for CTX-VCR patients. Two-year survivals were 4 and 9%, respectively. Neurotoxicity was the main toxic manifestation in both treatment groups. Severe peripheral neuropathy (grade 4, World Health Organization [WHO]) did not occur with either drug regimen. Treatment was discontinued because of grade 2-3 neuropathy in one patient after 6 cycles of CTX-VCR and in five patients after 1-6 cycles of CTX-VDS.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Radiation pneumonitis and fibrosis following split-course radiation therapy for lung cancer. A radiologic and physiologic study.

Radiographic signs of radiation pneumonitis and fibrosis were assessed and pulmonary function monitored in lung cancer patients after two different split-course radiation therapy schedules, one with a rest interval of 3 weeks and the other with a rest interval of 5 weeks, the total radiation dose being the same in both treatments (55 Gy/20 fractions/7 or 9 weeks). Post-mortem findings were analysed when available. Spirometric measurement of vital capacity, determination of diffusing capacity for carbon monoxide (DL) and alveolar volume with the single breath technique, and determination of regional distribution of lung perfusion by two different techniques, radiospirometry and gamma camera digital display following intravenous injection of 133Xe, were carried out before and at various times after the completion of irradiation. Of the physiologic parameters, only DL showed a significant decrease 6 as well as 9 months post-treatment (p less than 0.05). No difference between the two treatment schedules could be shown with regard to grade or time pattern of radiologic changes or decrease in DL. The findings suggest that measurement of DL may be of value in monitoring patients included in research protocols for radiation therapy of lung cancer as well as in selection of patients for this treatment.

Aged↗
PubMed1986

Interferon-mediated in vivo induction of beta 2-microglobulin on small-cell lung cancers and mid-gut carcinoids.

Selected neuroendocrine tumors, such as small cell lung cancer (SCLC), and neuroblastoma express markedly diminished class I major histocompatibility complex (MHC) antigens (HLA framework and beta 2-microglobulin, beta 2m). Another neuroendocrine tumor, mid-gut carcinoid, also expresses reduced beta 2m antigen as demonstrated herein. Antigen expression is greatly enhanced on SCLC cell lines by in vitro exposure to interferon (IFN). To determine whether IFN mediates similar effects in vivo, we examined by immunoperoxidase staining beta 2m expression in paraffin-embedded tumor tissue sections obtained from 4 SCLC and 7 mid-gut carcinoid patients before and after receiving partially purified human leukocyte IFN-alpha therapy. Before IFN treatment, 3/4 SCLC tumors and 5/7 mid-gut carcinoids did not express beta 2m. By contrast, all tumors showed considerable expression of beta 2m after IFN therapy. Induction of class I antigens on tumor cells deficient in such expression may be one mechanism by which IFN exerts antitumor effects. We believe this is the first report of in vivo induction of class I MHC antigens in epithelial tumor cells in humans.

Carcinoid Tumor↗
PubMed1985

A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy.

An anti-emetic drug, nabilone, a synthetic cannabinoid, has been compared with prochlorperazine in 24 lung cancer patients receiving cancer chemotherapy. Each of the drugs studied was given orally every 12 hours, starting the night before chemotherapy, during one of two consecutive identical chemotherapy cycles in accordance with a double-blind cross-over random order assignment. Single doses were 2 mg of nabilone, or 15 mg of prochlorperazine. The chemotherapeutic regimens given included the following drugs in various combinations: cis-platinum, vincristine, cyclophosphamide, adriamycin, vindesine, and etoposide (VP16). Nabilone was significantly superior to prochlorperazine in the reduction of vomiting episodes. Side effects, mainly vertigo, were evident in nearly half of the patients after nabilone, and three patients were withdrawn from the study due to decreased coordination and hallucinations after nabilone. Side effects from prochlorperazine were limited to mild drowsiness in one patient. Two-thirds of the patients preferred nabilone to prochlorperazine. We conclude that nabilone is a moderately effective anti-emetic drug, but that the unpredictability of its side effects call for careful patient information, especially with elderly outpatients. We recommend that at least after the first dose of nabilone, the patient should be kept under close observation during 4 hours.

Administration, Oral↗
PubMed1985

Memory and psychomotor impairment following high-dose interferon treatment in amyotrophic lateral sclerosis.

Patients with amyotrophic lateral sclerosis were treated with high-dose intravenous infusion of human leukocyte interferon for six days. Neuropsychological examinations were carried out before, during and after the treatment. Marked reversible dysfunction was detected in immediate memory functions, coordination of hand movements, and drawing. Motor perseveration, micrographia, and slowing of behaviour were also observed. Changes appeared four to 12 days after start of treatment, with the peak on days six to eight. Recovery was almost complete by day 15. Intellectual ability, as measured by three WAIS subtests, praxis of hand movements, visuognostic functions, speech, reading, writing, and calculation remained essentially unaffected. The profile of the neuropsychological deficits observed, the absence of defects typical of focal posterior cortical lesions, the simultaneously slowed electroencephalographic activity with frontal accentuation, and the increased central conduction times of brain stem auditory evoked potentials suggest frontobasal involvement.

Aged↗
PubMed1985

Human leukocyte interferon as part of a combined treatment for previously untreated small cell lung cancer.

Human leukocyte interferon, HuIFN-alpha (LE), has been tested in combination with radiotherapy and chemotherapy for previously untreated small cell lung cancer. Nine patients with limited disease received high-dose IFN followed by a low-dose regimen; and six patients had a low-dose regimen from the beginning. The high dosage of IFN consisted of 800 X 10(6) IU given as a continuous intravenous infusion for 5 days, followed by 6 X 10(6) IU i.m. three times weekly. If the first site of disease progression was local or in a central nervous system location, radiotherapy (55 Gy/20 F/7 weeks locally and/or 30 Gy/10 F/2 weeks whole brain) was applied and IFN was continued. Chemotherapy was administered only if there was disease dissemination outside the chest. Three patients achieved minor response for as long as 20, 25, and 42 weeks, respectively, with IFN alone. Three of five complete responders to IFN-radiotherapy died 18, 33, and 41 weeks from the start of IFN treatment without chemotherapy. Autopsy did not reveal macroscopic or microscopic tumor at any site, but there was severe radiation pneumonitis. Four of nine patients were administered chemotherapy subsequent to IFN-radiotherapy because of disease dissemination. The median length of survival of the entire group was 41 weeks. On the low-dose regimen, one patient achieved partial response with IFN alone (duration, 12 weeks); of five evaluable patients three achieved complete remission and two partial remission to IFN-radiotherapy, and one of the three complete responders to IFN-radiotherapy died of severe radiation pneumonitis at 21 weeks from the start of IFN treatment. No tumor was detected at autopsy. The study is in progress. Average survival at present is 33 weeks. The results derived from both our studies suggest a growth-delaying effect of HuIFN-alpha (Le) on small cell lung cancer. They also suggest potentiation of radiation by HuIFN-alpha (Le). Memory and psychomotor dysfunction, fatigue, and anorexia were dose limiting with both short-duration, high-dose and long-duration, low-dose IFN therapy. We feel that IFN, as part of a combined multimodality treatment of small cell lung cancer, may play a role by delaying metastatic dissemination.

Adult↗
PubMed1984

Bretylium in hypothermia-induced ventricular fibrillation in dogs.

We undertook a study to determine the ability of intravenous bretylium to cause "chemical defibrillation" or facilitate electrical defibrillation of hypothermia-induced ventricular fibrillation in the dog. Two groups of ten dogs were cooled to 22 C and placed into ventricular fibrillation. Following initiation of cardiopulmonary resuscitation, bretylium 15 mg/kg or normal saline was administered and the dogs were defibrillated according to a standard protocol. Both groups were equivalent in mean arterial pressure and arterial blood gases throughout the investigation. Seven dogs in each group were converted from ventricular fibrillation to an organized cardiac rhythm (P greater than .05). Despite the possible value of prophylactic bretylium in the setting of hypothermia, its use as active treatment for hypothermia-induced ventricular fibrillation in dogs does not seem to be beneficial.

Animals↗