Bo Littbrand

Effects of Sucralfate on Mucositis During and Following Radiotherapy of Malignancies in the Head and Neck Region: A double-blind placebo-controlled study

Radiotherapy of head and neck malignancies is accompanied by oral discomforts, such as epithelitis, pain and functional impairment. This can lead to chronic sequalae with subjective distress such as loss of taste and xerostomia and pronounced decrease in quality of life. Thus, the need to reduce the mucosal damage following radiotherapy is obvious. Therefore, we investigated the possible ability of sucralfate, an aluminium hydroxide complex of sulphated sucrose used in the treatment of gastric ulcer, in preventing oral discomfort in patients treated with curative intent for malignancies in the head and neck region. The study was double-blind, placebo-controlled and randomized and included 50 consecutive patients. The study demonstrated that the proportion of patients with severe mucosal reactions was significantly lower in the sucralfate group than in the placebo group.

Hyperfractionated Radiotherapy of Bladder Cancer: A ten-year follow-up of a randomized clinical trial

One hundred and sixty-eight patients with invasive bladder cancer, T2-T4, were randomized to one of two treatments; hyperfractionation with 1 Gy 3 times a day to a total of 84 Gy or conventional treatment 2 Gy once a day to a total of 64 Gy. Both treatments were given over 8 weeks with a rest interval of 2 weeks in the middle of the treatment period. The present report included all patients after a follow-up period of at least 10 years. The survival benefit from hyperfractionation previously reported after 5 years is still evident after 10 years. The effect was detectable in all three subsets (T2, T3 and T4) and in the pooled data. However, it only reached statistical significance in the T3 subset and in the total pooled data set. Local control was also assessed by cystoscopy and cytology on bladder washouts. An improvement in local control was seen at all follow-up intervals and at all times out to 10 years but the differences were not statistically significant due to the falling number of patients available for assessment. Complications in the bowel requiring surgical treatment were more common in the hyperfractionated group but the difference was not significant since this group consisted of a greater number of patients alive and therefore at risk. This trial showed that the benefit of the hyperfractionated schedule persisted over a 10-year follow-up period, both for local control and survival.

Acute Effects of Accelerated Radiotherapy in Combination with Carbogen Breathing and Nicotinamide (Arcon)

Combining accelerated radiotherapy with carbogen and nicotinamide (NAM) has been proposed as a strategy to overcome the sparing effect of tumour clonogen repopulation and hypoxia. Six patients with squamous cell carcinomas of the head and neck were given accelerated radiotherapy, carbogen breathing and high dose nicotinamide in order to evaluate the feasibility of this treatment regimen. The patients received radiotherapy in two daily fractions of 1.8-1.9 Gy, five days/week, total dose 54-57.6 Gy, in an overall treatment time of 19-22 days. The interfraction intervals were 7-8 hours between the two fractions on the same day. Carbogen breathing was started 5 minutes before and went on during each radiation fraction. a variety of NAM doses were administered orally in conjunction with radiation therapy and analyses of plasma concentrations of NAM and its metabolites were performed. The most common side-effect from NAM was nausea and vomiting, which in one case hampered further NAM administration. The side effects were not related to plasma levels of NAM or its main metabolites. Additionally, one patient with preexisting heart disease developed a severe hypotension and renal dysfunction. All acute reactions healed without further complications. The mucosal reactions were generally brisk. Thus, the combination of accelerated radiotherapy with carbogen and NAM seems to be tolerable.

Planning of radiotherapy for patients with hip prosthesis

The effects of a hip prosthesis on the dose distribution when treating pelvic cancer have been evaluated. A prosthesis of titanium alloy in a water phantom was used as a model. Photon radiation beams with energies of 6, 20, and 50 MV and with a focus phantom distance of 100 cm were directed against the prosthesis. The dose profiles at different depths were measured with the RFA-7 system. The sphere of the prosthesis was inhomogeneous. The dose in a beam behind the prosthesis was reduced with the order of 10-40% and the largest distortion was behind the shaft. Using an opposed four-field technique with the same weight on all the fields, the dose reduction was as large as 7-12% in a string across the target behind the end of the shaft. With 50% weight on the lateral fields, the dose reduction was 4-8% of the average dose. Such an uneven dose distribution may decrease the curability, and a treatment technique not including the prosthesis should be preferred. Finally, a local increase of the dose close to the prosthesis seems to be of limited practical concern even at the highest energies.

Prevention and Therapy of Radiation-Induced Bowel Discomfort

In a double-blind randomized placebo-controlled study, including 70 patients treated with radiotherapy of localized malignancies in the pelvis, the effects of prophylactic sucralfate in preventing bowel discomfort were evaluated. Radiotherapy was delivered in a conventional manner with high-energy photons in a total dose of 62-66 Gy (target dose, 1.8-2.2 Gy) during 6.5 weeks. Dose granules of sucralfate or placebo were given 2 weeks after irradiation started and continued for 6 weeks. All analyses were performed blindly. The patients in the sucralfate group had significantly less problems with acute (5 weeks) and chronic (66 weeks) bowel discomfort. The consumption of loperamide was also reduced in the sucralfate group, and the weight decrease was less pronounced. No adverse effects were seen. Thus, sucralfate seems to be beneficial in minimizing the problems of bowel discomfort during and after irradiation of malignancies in the pelvis. These results are discussed in relation to other related observations.

Fractionated-irradiation and late changes in rat parotid-gland : effects on the number of acinar-cells, potassium efflux, and amylase secretion

Irradiation of head- and neck cancer commonly results in oral dryness and discomfort for the patients due to salivary gland damage. The exact mechanisms behind the inherent radiosensitivity of salivary glands remain to be elucidated. In the present study, we used different in vitro secretory models and quantitative morphological characterization of rat parotid gland following fractionated unilateral irradiation to one gland on a 5-day fraction schedule (Monday-Friday) with 6 MV photons (total dose 30, 35, 40 and 45 Gy) or a two-fractions regimens in 5 days (Monday and Friday) with total dose of 24 and 32 Gy. The contralateral shielded gland served as control, and parallel analyses of irradiated and control glands were performed 180 days following the last irradiation treatment. The relative noradrenaline stimulated electrolyte secretion (86rubidium tracer for potassium) was decreased in the irradiated compared with control glands. The noradrenaline-stimulated exocytotic amylase release was not significantly affected by irradiation, but the gland content of amylase was decreased dose-dependently. The quantitative morphological analysis revealed a dose-dependent decline in the number of acinar cells, whereas the other parenchymal cells (intercalated, striated- and excretory duct cells) were unaffected by the irradiation compared with control glands.

Prevention of irradiation-induced bowel discomfort by sucralfate: A double-blind, placebo-controlled study when treating localized pelvic cancer

Sucralfate, an aluminum hydroxide complex of sulfated sucrose used in the treatment of gastric ulcer, was shown to prevent irradiation-induced diarrhea and bowel discomfort significantly in patients treated for pelvic cancer with external radiotherapy with intent to cure. The double-blind placebo-controlled study included 70 patients with carcinoma of the prostate and urinary bladder without distant metastasis (T1-4NO1xMO) and performance status of greater than or equal to 90% Karnofsky scale. Radiotherapy was administered in a conventional manner with MeV photons and a four-field technique. The total dose was 62-66 Gy and total treatment time of 6.5 weeks. Dose granules of sucralfate or placebo were dispensed to each patient 2 weeks after radiation started and continued for 6 weeks. All analyses were performed blindly. Seven of 34 evaluable patients in the placebo group and 18 of 32 evaluable patients in the sucralfate group did not present with diarrhea during the observation period. The frequency of defecation and stool consistency were significantly improved by sucralfate. Fourteen patients in the placebo group and only three in the sucralfate group required symptomatic therapy with loperamide. There was no evidence of adverse effects associated with the use of sucralfate. Sucralfate can be of beneficial value in diminishing the bowel discomfort during radiotherapy of pelvic malignancies, and the earlier proposed mechanisms of action (e.g., protection of denuded mucosa, cytoprotective properties, binding bile acids) can also be valid for the current effects of sucralfate.

Daily-diary evaluated side-effects of conformal versus conventional prostatic cancer radiotherapy technique

Conventional 4-field box radiotherapy technique induces high morbidity for patients with localized prostatic cancer. Using a patient daily diary, the present study compared side-effects after conventional radiotherapy with conformal radiotherapy for prostate cancer. Fifty-eight patients treated with the conventional technique (with or without sucralfate) were compared with 72 patients treated with conformal technique. The patient groups were compared with an age-matched control population. Patients treated with conformal technique were also evaluated regarding acute and late urinary problems. Results showed that patients treated with conformal technique reported significantly fewer side-effects as compared with conventional technique. Patients treated with sucralfate also showed slightly decreased intestinal morbidity in comparison to non-sucralfate group. Acute and late morbidity evaluated by the patients was decreased after conformal radiotherapy as compared with the conventional technique. Sucralfate may be of value if conformal radiotherapy is used for dose escalation in prostatic cancer patients.

Hypoxia, Normoxia and Hyperoxia: Terminology for Medical In Vitro Cell Biology

From the Danish Cancer Society, Department of Virus and Cancer, Aarhus, Denmark (P. Ebbesen, V. Zachar), Department of Biophysics, Research Section for Plasma and Space Physics, University of Oslo, Norway (E.O. Pettersen), Department of Oncology, Umeå University, Sweden (J. Denekamp, B. Littbrand), Department of Virology, The Haartman Institute, University of Helsinki, Finland (J. Keski-Oja), Royal Danish School of Pharmacy, Institute of Pharmacology, Copenhagen, Denmark (Arne Schousboe), Faculty of Medicine, Department of Pharmacology and Toxicology, NTNU Trondheim (U. Sonnewald) and the Department of Cell Biology, The Norwegian Radium Hospital, Montebello, Oslo, Norway (Øystein A, mellem)From the Danish Cancer Society, Department of Virus and Cancer, Aarhus, Denmark (P. Ebbesen, V. Zachar), Department of Biophysics, Research Section for Plasma and Space Physics, University of Oslo, Norway (E.O. Pettersen), Department of Oncology, Umea University, Sweden (J. Denekamp, B. Littbrand), Department of Virology, The Haartman Institute, University of Helsinki, Finland (J. Keski-Oja), Royal Danish School of Pharmacy, Institute of Pharmacology, Copenhagen, Denmark (Arne Schousboe), Faculty of Medicine, Department of Pharmacology and Toxicology, NTNU Trondheim (U. Sonnewald) and the Department of Cell Biology, The Norwegian Radium Hospital, Montebello, Oslo, Norway (Oystein A, mellem)

Sucralfate: Prophylaxis of Mucosal Damage During Cancer Therapy

BACKGROUND Chemotherapy and radiotherapy of different malignancies may be complicated by a variety of side effects, some of which may be related mucosal damage. RESULTS There is increasing evidence that sucralfate reduces the severity of radiation-induced mucositis in the head and neck, esophagus, and the lower gastrointestinal tract. Sucralfate also seems to protect the skin during radiotherapy and to reduce chemotherapy-induced mucositis. CONCLUSION Further studies could be of interest to define the clinical significance of sucralfate in reducing the mucosal damage and increasing quality of life during an following cancer therapy.