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32 Amifostine protects from acute toxicity patients with cancer of the cervix treated with radiochemotherapy
Discussion of Proffered Papers
Sunday, l0 December 2000
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controlled cohort than the population comprising this report. Conclusion: Acupuncture may provide relief for patients with xerostomia post-radiation therapy who are otherwise refractory to pilocarpine therapy. 32
Amifostine protects from acute toxicity patients with cancer of the cervix treated with radiochemotherapy D. Antonadou, P. Komi, A. Petridis, M. Synodinou, N. Throuvalas Radiation Oncology Department, Metaxas Cancer Hospital, Radiotherapy, Piraeus, Greece Radiation therapy (XRT) has been the standard treatment with curative intent for patients with locally advanced cancer of the cervix ,but the incidence of recurrences is high.There is an increasing interest in combining radical XRT with systemic treatment with a view to either sterilizing micro metastases or enhancing the therapeutic effect on the local tumor control through radiosensitization. An enhancement of normal tissue injury will often accompany the therapeutic effect thus reducing or eliminating the final gain. Radiation injury of the intenstine or bladder have been recognized as important complications that might affect the patient's quality of life.When chemotherapy and radiotherapy are combined the net effect may be additive, synergistic or subadditive. The aim of the current approaches is treatment intensification to achieve maximum cell kill. However this strategy is feasible only if normal tissues can be protected selectively. To this end Amifostine which is a thio-organic compound that is selectively taken by normal tissues but enters most tumor cells only by passive diffusion can selectively protect normal cells from the cytotoxic and mutagenic effects of radiation and chemotherapy and reduce acute and late toxicities. The objective of this clinical trial was to investigate whether pretreatment with Amifostine could reduce the incidence of acute toxicities during concurrent radiochemotherapy (RCT) with Carboplatin in patients with Stage lib or III cancer of the cervix. Materials and methods: Between July 1998 to February 2000 35 patients with histologically proven cancer of the cervix were entered in this trial (22 stage lib, 13 stage III) All patients underwent staging procedure. The eligibility criteria were histologically confirmed cancer of the cervix, ECOG performance status 0-1, no prior chemotherapy o radiotherapy was allowed,written informed consent.Study endpoints were the incidence of gastrointenstinal or/and genitourinary toxicity acute toxicity . Haematological toxicity as well as tumor response to RCT were evaluated. All patients underwent external beam radiotherapy with 18MV photon beam with four fields (box technique) to the pelvis, to a total dose of 54 Gy, 2Gy daily dose/5 days/week, which was followed up by intracavitary insertion, with a total dose of 10-15 Gy to point A. All patients received 90mg/m2 Carboplatin once per week during the 5-6 weeks of XRT, they received also 340mg/sqm Amifostine daily 15 -20minutes before XRT. Acute toxicities were graded according the RTOG/EORTC criteria. All patients were evaluated once per week during treatment. Complete history was taken, physical examination was performed and blood counts were measured. Response to treatment was assessed 6 weeks post RCT with clinical examination and CT scan of the abdomen and pelvis using the World Health Organization criteria for response. Results: All patients completed treatment without delay. None of the patients experienced grade 3 haematological toxicity.Grade 2 thrombocytopenia was present in 10 patients(35%). Acute toxicities were mainly present during week 4 and 5. Grade 3 genitourinary toxicity was present in 5 patients (14%) and grade 3 gastrointenstinal toxicity in 9 patients (25.7%). There were 31/35 (88.5%) complete and partial responses. Patients are followed up for evaluation of late toxicities and duration of response. in conclusion Amifostine allowed completion of the planned RCT treatment without delay, the number of patients experiencing acute toxicity was acceptable. A larger randomized trial will probably confirm the above promising results. 33
Does pilocarpine treatment improve subjective quality of life and zerostomia in head and neck cancer patients following radical radiotherapy? D. McCarthy, D. Waldron, M. Moriarty 1Dental College, Dental, Dublin, Ireland 2University College Hospital, Palliative Medicine, Galway, Ireland 3St Lukes Hospital, Radiotherapy, Dublin, Ireland Background and aims: Xerostomia is a major complaint associated with salivary gland dysfunction secondary to therapeutic radiation in head and neck cancer patients. This lack of saliva can be associated with resulting poor oral comfort, increased incidence and severity of dental caries and problems with chewing, swallowing and speaking. Remedies to date have been largely ineffective. A number of double-blind studies have suggested that the cholinergic parasympathomimetic agent Pilocarpine Hydrochloride can improve saliva secretion. This study investigates the impact of this drug on patients' Quality of Life, salivary flow rate and xerostomia questionnaire. Subjects and methods: The study population comprised 22 patients (17 male, 5 female, mean age 60, median age 63, S.D. 12.97) with a history of radical external beam radiotherapy, using 4 MV photons, for histologically proven Head and Neck epithelial malignancies. A prospective double-blind cross-over design was used. Patients were randomised to 2 groups. Group A received Pilocarpine 5 mgs T.D.S. for 3 months. Group B received a placebo T.D.S. for 3 months. The groups then crossed over for a further period of 3 months. Patients were assessed at each of 5 visits; at 0, 42, 90, 132 and 180 using the Schedule for the Evaluation of Individual Quality of Life (SEIQoL). Resting and stimulated, salivary flow rates were assessed at each visit and a xerostomia questionnaire completed. Results: a. 19/22 patients were able to attend for all 5 assessments of quality of life (SEIQoL). The mean time from diagnosis to start of trial was 56 months (median 33, $.D. 65.41, range 12-240 months). The primary site of disease comprised a number of head and neck cancer sites. Using linear regression analysis of global QoL score from SEIQoL-DW on all visits and taking into account association with initial treatment, association with placebo and Pilocarpine it was seen that there was insignificant variation in QoL scores within each group on each visit. b. on analysis of effect of Salagen on resting saliva and stimulated saliva flow rates, there was no order effect with any of these variables, i.e. there was no effect of Salagen dependent on whether it was administered first or second, in fact there was a shortage of any effect. For resting saliva, n=22, mean 0.06, SD 0.11, Min -0.10, 25th centile 0.00, Median 0.03, 75th centile 0.09. For stimulated saliva, n=22, mean 0.06, SD 0.23, Min -0.42, 25th centile -0.06, Median -0.02, 75th centile 0.18. As can be seen from the above results, the mean difference between treatment and control is close to zero in all cases.
Sunday, l0 December 2000
$31
controlled cohort than the population comprising this report. Conclusion: Acupuncture may provide relief for patients with xerostomia post-radiation therapy who are otherwise refractory to pilocarpine therapy. 32
Amifostine protects from acute toxicity patients with cancer of the cervix treated with radiochemotherapy D. Antonadou, P. Komi, A. Petridis, M. Synodinou, N. Throuvalas Radiation Oncology Department, Metaxas Cancer Hospital, Radiotherapy, Piraeus, Greece Radiation therapy (XRT) has been the standard treatment with curative intent for patients with locally advanced cancer of the cervix ,but the incidence of recurrences is high.There is an increasing interest in combining radical XRT with systemic treatment with a view to either sterilizing micro metastases or enhancing the therapeutic effect on the local tumor control through radiosensitization. An enhancement of normal tissue injury will often accompany the therapeutic effect thus reducing or eliminating the final gain. Radiation injury of the intenstine or bladder have been recognized as important complications that might affect the patient's quality of life.When chemotherapy and radiotherapy are combined the net effect may be additive, synergistic or subadditive. The aim of the current approaches is treatment intensification to achieve maximum cell kill. However this strategy is feasible only if normal tissues can be protected selectively. To this end Amifostine which is a thio-organic compound that is selectively taken by normal tissues but enters most tumor cells only by passive diffusion can selectively protect normal cells from the cytotoxic and mutagenic effects of radiation and chemotherapy and reduce acute and late toxicities. The objective of this clinical trial was to investigate whether pretreatment with Amifostine could reduce the incidence of acute toxicities during concurrent radiochemotherapy (RCT) with Carboplatin in patients with Stage lib or III cancer of the cervix. Materials and methods: Between July 1998 to February 2000 35 patients with histologically proven cancer of the cervix were entered in this trial (22 stage lib, 13 stage III) All patients underwent staging procedure. The eligibility criteria were histologically confirmed cancer of the cervix, ECOG performance status 0-1, no prior chemotherapy o radiotherapy was allowed,written informed consent.Study endpoints were the incidence of gastrointenstinal or/and genitourinary toxicity acute toxicity . Haematological toxicity as well as tumor response to RCT were evaluated. All patients underwent external beam radiotherapy with 18MV photon beam with four fields (box technique) to the pelvis, to a total dose of 54 Gy, 2Gy daily dose/5 days/week, which was followed up by intracavitary insertion, with a total dose of 10-15 Gy to point A. All patients received 90mg/m2 Carboplatin once per week during the 5-6 weeks of XRT, they received also 340mg/sqm Amifostine daily 15 -20minutes before XRT. Acute toxicities were graded according the RTOG/EORTC criteria. All patients were evaluated once per week during treatment. Complete history was taken, physical examination was performed and blood counts were measured. Response to treatment was assessed 6 weeks post RCT with clinical examination and CT scan of the abdomen and pelvis using the World Health Organization criteria for response. Results: All patients completed treatment without delay. None of the patients experienced grade 3 haematological toxicity.Grade 2 thrombocytopenia was present in 10 patients(35%). Acute toxicities were mainly present during week 4 and 5. Grade 3 genitourinary toxicity was present in 5 patients (14%) and grade 3 gastrointenstinal toxicity in 9 patients (25.7%). There were 31/35 (88.5%) complete and partial responses. Patients are followed up for evaluation of late toxicities and duration of response. in conclusion Amifostine allowed completion of the planned RCT treatment without delay, the number of patients experiencing acute toxicity was acceptable. A larger randomized trial will probably confirm the above promising results. 33
Does pilocarpine treatment improve subjective quality of life and zerostomia in head and neck cancer patients following radical radiotherapy? D. McCarthy, D. Waldron, M. Moriarty 1Dental College, Dental, Dublin, Ireland 2University College Hospital, Palliative Medicine, Galway, Ireland 3St Lukes Hospital, Radiotherapy, Dublin, Ireland Background and aims: Xerostomia is a major complaint associated with salivary gland dysfunction secondary to therapeutic radiation in head and neck cancer patients. This lack of saliva can be associated with resulting poor oral comfort, increased incidence and severity of dental caries and problems with chewing, swallowing and speaking. Remedies to date have been largely ineffective. A number of double-blind studies have suggested that the cholinergic parasympathomimetic agent Pilocarpine Hydrochloride can improve saliva secretion. This study investigates the impact of this drug on patients' Quality of Life, salivary flow rate and xerostomia questionnaire. Subjects and methods: The study population comprised 22 patients (17 male, 5 female, mean age 60, median age 63, S.D. 12.97) with a history of radical external beam radiotherapy, using 4 MV photons, for histologically proven Head and Neck epithelial malignancies. A prospective double-blind cross-over design was used. Patients were randomised to 2 groups. Group A received Pilocarpine 5 mgs T.D.S. for 3 months. Group B received a placebo T.D.S. for 3 months. The groups then crossed over for a further period of 3 months. Patients were assessed at each of 5 visits; at 0, 42, 90, 132 and 180 using the Schedule for the Evaluation of Individual Quality of Life (SEIQoL). Resting and stimulated, salivary flow rates were assessed at each visit and a xerostomia questionnaire completed. Results: a. 19/22 patients were able to attend for all 5 assessments of quality of life (SEIQoL). The mean time from diagnosis to start of trial was 56 months (median 33, $.D. 65.41, range 12-240 months). The primary site of disease comprised a number of head and neck cancer sites. Using linear regression analysis of global QoL score from SEIQoL-DW on all visits and taking into account association with initial treatment, association with placebo and Pilocarpine it was seen that there was insignificant variation in QoL scores within each group on each visit. b. on analysis of effect of Salagen on resting saliva and stimulated saliva flow rates, there was no order effect with any of these variables, i.e. there was no effect of Salagen dependent on whether it was administered first or second, in fact there was a shortage of any effect. For resting saliva, n=22, mean 0.06, SD 0.11, Min -0.10, 25th centile 0.00, Median 0.03, 75th centile 0.09. For stimulated saliva, n=22, mean 0.06, SD 0.23, Min -0.42, 25th centile -0.06, Median -0.02, 75th centile 0.18. As can be seen from the above results, the mean difference between treatment and control is close to zero in all cases.