114
You suggest that the protocol of the trial of screening in women 40-41 in Britain may need modification in the light of the Canadian results. The only lesson to be learnt is the overriding importance of continual quality control.
aged
MRC Biostatistics Unit, UK
Cambridge CB2 2BW,
NICHOLAS E. DAY STEPHEN W. DUFFY
1. Baines
CJ, Miller AB, Kopans DB, et al. Canadian breast screening study: assessment of technical quality by external review. Am J Roentgenol 1990; 155: 743-47. 2. Miller AB, Baines CJ, To T, Wall C. The Canadian National Breast Screening Study. In: Miller AB, Chamberlain J, Day NE, Hakama M, Prorok PC, eds. Cancer screening. Cambridge: Cambridge University Press (in press). 3. Day NE. Screening for breast cancer. Br Med Bull 1991; 47: 400-15.
Tamoxifen to prevent breast cancer S!R,—The participation of premenopausal women in a trial of tamoxifen for the prevention of breast cancer is questioned by Dr Spicer and colleagues (June 8, p 1414) because of the risk of induction of ovarian cancer. Although we agree that caution is needed in asking well women to take part in such a study, especially those in the younger age group, there does not seem to be any clinical evidence to suggest that the postulated biological actions on the ovary cause serious difficulties. Worldwide, over 8500 premenopausal women (in fact those aged under 50) have been randomised to trials of adjuvant tamoxifen after treatment for primary breast cancer and of these about one-third did not receive any adjuvant chemotherapy. At the overview analysis by the Early Breast Cancer Trialist Collaborative group at its meeting in Oxford in September, 1990, there was no evidence of an increased risk of non-breast cancers for the tamoxifen-treated group, although this was not looked at in great detail. In the CRC Adjuvant Breast Trial, which randomised 676 premenopausal women between tamoxifen (353) and control (323), no excess ovarian cancers have been reported. Half the patients received postoperative cyclophosphamide 5 mg/kg daily for six days and tamoxifen was scheduled for two years at 20 mg daily. With a median follow-up of almost eight years only three ovarian tumours have been reported and all these are in the non-tamoxifen treated patients. To ensure that we are not missing information on these events a detailed questionnaire on medical conditions developing subsequent to the breast cancer is being completed by clinicians on all patients who are alive and breast-cancer free at the current time. This should enable us to determine whether any increased risk is evident in this group of patients. CRC Clinical Trials Centre, King’s College School of Medicine and Dentistry,
that conventional treatments are not suitable for or are less useful in older patients. In general fitness-especially mental, psychological,
and physiological-elderly patients are better than in former decades in Europe, so that more elderly patients with cancer will now be suitable for optimum cancer therapy. As part of the evaluation of cancer treatments in older patients, quality-of-life measures should be routine. Early diagnosis is just as important in the old as in younger groups, especially for cancers of the breast and colon. Elderly people are seldom the target of campaigns and tend to be excluded from screening projects but the biology of tumours in the elderly is no different, and certainly no less aggressive, than that in younger
patients. There are few data on chemotherapy and radiotherapy in elderly patients, and this area of clinical research should be improved. Surgery should always be considered as first-line therapy for solid tumours in elderly patients as in younger ones. In some diseases such as non-Hodgkin lymphoma and acute leukaemia, specific regimens have been developed, not with the intention of undertreating elderly patients but to provide adequate and acceptable therapy for patients for whom aggressive chemotherapy is likely to be unsafe. A major focus of research should be the establishment of a scale of
frailty so that treatments can be selected for different stages. The three major issues raised in this consensus were: (1) Chronological age should not be used to exclude patients from early diagnosis programmes, screening projects, or trials of treatment
Centro di Riferimento
Rayne Institute,
JOAN HOUGHTON
London SE5 9NU, UK
DIANA RILEY
Oncologico,
(PN), Italy
U. TIRELLI
Hôpital Cantonal Universitaire, Geneva
M. AAPRO
33081 Aviano
Kantonsspital, Basel
R. OBRIST
Katholieke Universiteit, Nijmegen
J. FESTEN
Centre Antoine Laccassagne, Nice
M. SCHEIDER
Guy’s Hospital,
I. FENTIMAN
London
Centro di Riferimento
1. Fentiman
MICHAEL BAUM
for cancer.
(2) All treatment modalities should be offered to elderly patients. (3) Great effort should be made to establish quality-of-life measures in elderly patients.
S. MONFARDINI
Oncologico, Aviano
I, Tirelli U, Monfardini S, elderly? Lancet 1990; 335: 1020-22.
et
al.
Why
Adverse reactions with Cancer treatment and old
people
SiR,—In April, 1990, we discussed in The Lancet problems related to the management of cancer in the elderly/ and announced a joint EORTC/National Cancer Institute meeting. This was held last October at San Servolo Island, Venice. A European Community Working Party on Neoplasia in the Elderly was appointed on Oct 16. This was sponsored by Directorate General XII of the EC as part of the programme Europe against Cancer. What follows is that working-party’s consensus on a strategy for cancer treatment in the elderly. Epidemiological data point to a significant increase in cancer patients over the age of 70 years in Europe in the 1990s. Better diagnostic techniques and treatments for elderly patients are needed urgently because cancer-related survival of these patients is lower than it is in younger patients with malignant disease. In the management of elderly patients there should be no discrimination based on age alone. Education programmes should be addressed to general practitioners and specialists to convince them that surgery, radiotherapy, and chemotherapy should be considered when necessary in all cancer patients irrespective of age. In EC countries the referral rate of elderly patients to cancer centres tends to be lower than that for younger patients because most physicians feel
is
cancer so
badly treated in the
anistreplase
SIR,-Anisoylated human plasminogen streptokinase activator complex (APSAC, anistreplase) reduces mortality in patients with acute myocardial infarction. However, the value of this thrombolytic agent as a treatment for acute massive pulmonary embolism (AMPE) is not yet fully established.2 We have recently taken part in a European open pilot study on the effects of 30 U anistreplase given intravenously as a 5 min infusion in patients with AMPE. The trial was stopped after 9 patients were treated because 3 had episodes of severe hypotension. No patient had pre-existing cardiopulmonary disease, and none had previously received a thrombolytic drug or had any contraindication to such therapy. Case 1-A 35-year-old woman was admitted with AMPE. Mean pulmonary artery pressure (PAP) was 43 mm Hg, cardiac index (CI) 3111 solidus min per m2, and total pulmonary vascular resistance (TPVR) 14 IU/mZ. 4 min after anistreplase infusion, she complained of malaise and sweating. Tachycardia was followed by bradycardia (heart rate 40/min) and a seizure. She was successfully resuscitated and 19 h after thrombolysis mean PAP and TPVR were 15 mm Hg and 4 IU/m2, respectively. Case 2-A 69-year-old-woman presented with AMPE. She had moderate increases in mean PAP (19 mm Hg) and TPVR (8 IU 1m2). 5 min after the end of anistreplase infusion, she felt faint, and her blood pressure fell from 127/80 to 83/53 mm Hg, but
You suggest that the protocol of the trial of screening in women 40-41 in Britain may need modification in the light of the Canadian results. The only lesson to be learnt is the overriding importance of continual quality control.
aged
MRC Biostatistics Unit, UK
Cambridge CB2 2BW,
NICHOLAS E. DAY STEPHEN W. DUFFY
1. Baines
CJ, Miller AB, Kopans DB, et al. Canadian breast screening study: assessment of technical quality by external review. Am J Roentgenol 1990; 155: 743-47. 2. Miller AB, Baines CJ, To T, Wall C. The Canadian National Breast Screening Study. In: Miller AB, Chamberlain J, Day NE, Hakama M, Prorok PC, eds. Cancer screening. Cambridge: Cambridge University Press (in press). 3. Day NE. Screening for breast cancer. Br Med Bull 1991; 47: 400-15.
Tamoxifen to prevent breast cancer S!R,—The participation of premenopausal women in a trial of tamoxifen for the prevention of breast cancer is questioned by Dr Spicer and colleagues (June 8, p 1414) because of the risk of induction of ovarian cancer. Although we agree that caution is needed in asking well women to take part in such a study, especially those in the younger age group, there does not seem to be any clinical evidence to suggest that the postulated biological actions on the ovary cause serious difficulties. Worldwide, over 8500 premenopausal women (in fact those aged under 50) have been randomised to trials of adjuvant tamoxifen after treatment for primary breast cancer and of these about one-third did not receive any adjuvant chemotherapy. At the overview analysis by the Early Breast Cancer Trialist Collaborative group at its meeting in Oxford in September, 1990, there was no evidence of an increased risk of non-breast cancers for the tamoxifen-treated group, although this was not looked at in great detail. In the CRC Adjuvant Breast Trial, which randomised 676 premenopausal women between tamoxifen (353) and control (323), no excess ovarian cancers have been reported. Half the patients received postoperative cyclophosphamide 5 mg/kg daily for six days and tamoxifen was scheduled for two years at 20 mg daily. With a median follow-up of almost eight years only three ovarian tumours have been reported and all these are in the non-tamoxifen treated patients. To ensure that we are not missing information on these events a detailed questionnaire on medical conditions developing subsequent to the breast cancer is being completed by clinicians on all patients who are alive and breast-cancer free at the current time. This should enable us to determine whether any increased risk is evident in this group of patients. CRC Clinical Trials Centre, King’s College School of Medicine and Dentistry,
that conventional treatments are not suitable for or are less useful in older patients. In general fitness-especially mental, psychological,
and physiological-elderly patients are better than in former decades in Europe, so that more elderly patients with cancer will now be suitable for optimum cancer therapy. As part of the evaluation of cancer treatments in older patients, quality-of-life measures should be routine. Early diagnosis is just as important in the old as in younger groups, especially for cancers of the breast and colon. Elderly people are seldom the target of campaigns and tend to be excluded from screening projects but the biology of tumours in the elderly is no different, and certainly no less aggressive, than that in younger
patients. There are few data on chemotherapy and radiotherapy in elderly patients, and this area of clinical research should be improved. Surgery should always be considered as first-line therapy for solid tumours in elderly patients as in younger ones. In some diseases such as non-Hodgkin lymphoma and acute leukaemia, specific regimens have been developed, not with the intention of undertreating elderly patients but to provide adequate and acceptable therapy for patients for whom aggressive chemotherapy is likely to be unsafe. A major focus of research should be the establishment of a scale of
frailty so that treatments can be selected for different stages. The three major issues raised in this consensus were: (1) Chronological age should not be used to exclude patients from early diagnosis programmes, screening projects, or trials of treatment
Centro di Riferimento
Rayne Institute,
JOAN HOUGHTON
London SE5 9NU, UK
DIANA RILEY
Oncologico,
(PN), Italy
U. TIRELLI
Hôpital Cantonal Universitaire, Geneva
M. AAPRO
33081 Aviano
Kantonsspital, Basel
R. OBRIST
Katholieke Universiteit, Nijmegen
J. FESTEN
Centre Antoine Laccassagne, Nice
M. SCHEIDER
Guy’s Hospital,
I. FENTIMAN
London
Centro di Riferimento
1. Fentiman
MICHAEL BAUM
for cancer.
(2) All treatment modalities should be offered to elderly patients. (3) Great effort should be made to establish quality-of-life measures in elderly patients.
S. MONFARDINI
Oncologico, Aviano
I, Tirelli U, Monfardini S, elderly? Lancet 1990; 335: 1020-22.
et
al.
Why
Adverse reactions with Cancer treatment and old
people
SiR,—In April, 1990, we discussed in The Lancet problems related to the management of cancer in the elderly/ and announced a joint EORTC/National Cancer Institute meeting. This was held last October at San Servolo Island, Venice. A European Community Working Party on Neoplasia in the Elderly was appointed on Oct 16. This was sponsored by Directorate General XII of the EC as part of the programme Europe against Cancer. What follows is that working-party’s consensus on a strategy for cancer treatment in the elderly. Epidemiological data point to a significant increase in cancer patients over the age of 70 years in Europe in the 1990s. Better diagnostic techniques and treatments for elderly patients are needed urgently because cancer-related survival of these patients is lower than it is in younger patients with malignant disease. In the management of elderly patients there should be no discrimination based on age alone. Education programmes should be addressed to general practitioners and specialists to convince them that surgery, radiotherapy, and chemotherapy should be considered when necessary in all cancer patients irrespective of age. In EC countries the referral rate of elderly patients to cancer centres tends to be lower than that for younger patients because most physicians feel
is
cancer so
badly treated in the
anistreplase
SIR,-Anisoylated human plasminogen streptokinase activator complex (APSAC, anistreplase) reduces mortality in patients with acute myocardial infarction. However, the value of this thrombolytic agent as a treatment for acute massive pulmonary embolism (AMPE) is not yet fully established.2 We have recently taken part in a European open pilot study on the effects of 30 U anistreplase given intravenously as a 5 min infusion in patients with AMPE. The trial was stopped after 9 patients were treated because 3 had episodes of severe hypotension. No patient had pre-existing cardiopulmonary disease, and none had previously received a thrombolytic drug or had any contraindication to such therapy. Case 1-A 35-year-old woman was admitted with AMPE. Mean pulmonary artery pressure (PAP) was 43 mm Hg, cardiac index (CI) 3111 solidus min per m2, and total pulmonary vascular resistance (TPVR) 14 IU/mZ. 4 min after anistreplase infusion, she complained of malaise and sweating. Tachycardia was followed by bradycardia (heart rate 40/min) and a seizure. She was successfully resuscitated and 19 h after thrombolysis mean PAP and TPVR were 15 mm Hg and 4 IU/m2, respectively. Case 2-A 69-year-old-woman presented with AMPE. She had moderate increases in mean PAP (19 mm Hg) and TPVR (8 IU 1m2). 5 min after the end of anistreplase infusion, she felt faint, and her blood pressure fell from 127/80 to 83/53 mm Hg, but
