- Email: [email protected]
Ketanserin for hypertension after upper gastrointestinal surgery
1219
high level of seropositivity (6/58) was observed among Anonymous testing of more of the low-risk women in the second phase would have provided valuable information, since confirmation of the high observed seroprevalence rate (12-5%) would have important consequences for the sensitivity of a voluntary screening policy.
phase,
a
women who declined to be HIV tested.
Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, London WC1 E 7HT, UK
DAVID DUNN RICHARD HAYES
SIR,-Several UK hospitals are doing epidemiological studies, under the aegis of the Central Public Health Laboratory, Colindale, to find out the incidence of HIV infection in pregnant women. The testing is anonymous, and the only information recorded about the women is their racial origin. At St George’s Hospital, London, we book about 3500 women a year in the antenatal clinic (deliveries in 1990 were 3156). In the past fourteen months, we have tested blood samples from 4070 clinic attenders. 11were seropositive to HIV by the Abbott recombinant HIV-l/HIV-2 enzyme immunoassay. These positive tests were confirmed by the Central Public Health Laboratory. 2 other samples positive in our laboratory have not yet been checked. If they too are confirmed the seroprevalence rate will be 0-32%. We also have a high prevalence of hepatitis B carriage in our women (0-7%) and the data on HIV positivity accord with this. The seroprevalence rates are similar to those published by Heath et al from St Bartholomew’s Hospital in 1988.1 In 1987, we tested some 3000 antenatal women under the same conditions and found not 1 HIV seropositive. Thus, a substantial number of women booking at our clinics are seropositive to HIV. We also offer HIV testing on request and about 60 pregnant women were so tested in 1990, all being counselled before blood was taken. Only 2 were positive: on the assumption that these 2 were in the anonymous testing group, also, that would yield 11 other HIV-seropositive women about whom we did not know. These data have implications for the management of labour and post-partum care of mother and baby. Precautions against accidental infection of staff need to be tightened. We plan to increase the opportunities for women to be tested openly, but that means the provision of more counsellors in the antenatal clinics and increased resources in the virology laboratory. GEOFFREY CHAMBERLAIN
Departments of Obstetrics and Medical Microbiology, St George’s Hospital, London SW17 0RE, UK
JAMES BOOTH KEHINDE OMISAKIN HAROLD STERN
1. Heath RB, Grint PC, Hardiman AE. Anonymous testing of women attending antenatal clmics for evidence of infection with HIV. Lancet 1988; i: 1394.
SIR,-Dr Barbacci and colleagues argue in support of HIV antibody testing as a part of routine antenatal care. Such testing is already widespread, though in most areas it is of doubtful cost-benefit. As testing becomes more routine the associated counselling is likely to become truncated or non-existent. In my view Barbacci’s data can be interpreted as showing lack of value in extending HIV antibody testing to all women attending for antenatal care. Barbacci et al report that in Baltimore in the period before November, 1988, HIV antenatal screening, if restricted to women with a history of HIV risk, would have identified only 57% of HIV-seropositive women. Because testing was also made available to women without risk factors who wished to be tested, their programme in fact identified 83% of the HIV-positive women. (The remaining 17% were revealed by anonymous screening.) About one-third of women registering for antenatal care had a voluntary test for HIV. In November, 1988, a system which could be described as routine HIV antenatal testing was introduced; the number of voluntary HIV antibody tests increased to 76% and the proportion of all infected women who were identified in the voluntary programme rose to 87%. This increase in the yield of the voluntary programme (from 83% to 87%) was not significant. From November, 1988, among the women without risk factors
who declined testing a greater proportion were HIV positive than had been so earlier (6 out of 321 declining testing in the earlier period compared with 5 out of 40 in the later one). This decline in acceptance of HIV screening by women denying risk factors is significant (p<0001, X2). Perhaps women at risk in the earlier period had been prepared to accept testing though denying their risk status. The perceived hint of compulsion inherent in the later programme may have made such women more concerned about the consequences of a positive result. Either way in the high-risk Baltimore population, in which 4% of women are HIV positive, a sufficiently large number of HIV-positive women without risk factors will ask for HIV testing when this is not routine, so that the expansion of the programme does not appreciably increase the number of women testing positive. What is most important is the finding that a restriction of a programme to women with an identifiable risk factor, without extending it to other women requesting testing, would seriously underestimate the number of HIV-positive women. Fortunately, it is not the usual practice in which a truly voluntary programme is in place, for HIV testing not to be offered to any woman requesting it. It would be unfortunate ifBarbacci and colleagues’ interpretation that antenatal testing should be routine were to be extended from their high-risk population to low-risk populations such as most women in non-urban United States and women in Australia. Department of Immunology/Allergy, Prince of Wales Children’s Hospital,
JOHN B. ZIEGLER
Randwick, NSW 2031, Australia
Thrombotic thrombocytopenic purpura and
ticlopidine and
SIR,-Dr Page colleagues report (March 30, p 774) thrombotic thrombocytopenic purpura (TTP) after treatment with ticlopidine. Their finding contrasts with our experience1 and that of others2.3 that ticlopidine is beneficial in the treatment of TTP. We have seen two patients who after reaching complete remission with high-dose ticlopidine (750 mg daily) have been maintained at 250-500 mg daily for 38 and over 39 months, respectively, without relapse. It is difficult to explain the development of TTP after ticlodipine, which is known for its potent and unusual antiaggregating effect. TTP is usually a disease of the young adult, most commonly arising between age 30 and 40; curiously, three of Page and colleagues’ four patients were over 70. Perhaps these patients’ older age associated with impaired vascular conditions may have played a part in the pathophysiology of ticlopidine-associated TTP. We believe that these conflicting data are too few for the conclusion to be drawn that ticlopidine should not be used in patients with TTP.
Institute of Haematology "L. e A. Seràgnoli", Policlinico S Orsola, 40138 Bologna, Italy
NICOLA VIANELLI GIUSEPPE BANDINI LUCIA CATANI MONICA MATTIOLI BELMONTE LUIGI GUGLIOTTA
L, Mattioli Belmonte M, et al. Ticlopidine in the treatment of thrombotic thrombocytopenic purpura: report of two cases. Haematologica 1990;
1. Vianelli N, Catani
75: 274-77. 2. De Pasquale A, Venturoni LF, Paterlini P, et al. Possible usefulness of ticlopidine in combined treatment of thrombotic thrombocytopenic purpura: report of one case. Haematologica 1986; 71: 53-55. 3. Ishii Y, Ebata H, Satoh K. A case of thrombotic thrombocytopenic purpura, successful treatment by ticlopidine. Clin Hematol 1984; 25: 1097-102.
Ketanserin for hypertension after upper
gastrointestinal surgery SIR,-Dr Mikulic and colleagues (April 20, p 976) demonstrate
efficacy of ketanserin in the treatment of hypertension after gastrointestinal surgery. I disagree with their statement that the hypotensive action of ketanserin is attributable to its ability to act as an antagonist at peripheral postsynaptic serotonin (5-HT2) receptors. Ketanserin is not a specific antagonist at the 5-HTz the
1220
receptor, having a substantial affinity for both the ott-adrenoceptor and the histamine Hi receptor. The mechanism of the hypotension evoked by ketanserin and other 5-HT2 antagonists has been investigated by several workers,2,3 and the consensus of opinion is that the fall in blood pressure results from the ability of ketanserin to block oti-adrenoceptors within the central nervous system rather than its ability to block 5-HT2 receptors. Furthermore, the cardiovascular profile of ketanserin (ie, absence of reflex tachycardia and decrease in sympathetic nerve activity) is a feature of o-adrenoceptor antagonists such as prazosin and indoramin.4 Thus, ketanserin probably acts via the blockade of o-adrenoceptors, making prazosin and other antagonists of this site useful in the management of this particular form of hypertension. Section of Vascular Biology, MRC Clinical Research Centre, Harrow Middlesex HA1 3UJ, UK 1.
RICHARD G. BOGLE
Leysen JE, Awouters F, Kennis L, Lauduron PM, Vandenberg J, Janssen PAJ. Receptor binding profile of R41468, a novel antagonist at 5 HT2. Life Sci 1981; 28:
1015-22. JR. Mechanism of the hypotensive effect of ketanserin. J Cardiovasc Pharmacol 1982; 4: 829-38. 3. Ramage AG. Examination of the effects of some 5-HT2 antagonists on central sympathetic outflow and blood pressure in anaesthetised cats. NaunynSchmiedeberg’s Arch Pharmacol 1988, 338: 601-07 4. Ramage AG. The effect of prazosin, indoramin and phentolamine on sympathetic nerve activity. Eur J Pharmacol 1984; 106: 507-13. 2. Fozard
Medical
oncology in the 1990s
SIR,-Although I share some of Dr Braverman’s reservations (April 13, p 901) about the current role of cytotoxic chemotherapy for cancer, he paints an inaccurate picture. May I highlight one or two areas in which current research argues strongly against his nihilistic viewpoint. Braverman claims that "The apparent chemosensitivity of head and neck tumours is not reflected in survival benefits". Although the issue is far from settled, a prospective randomised study from the UKl has shown that the simple combination of methotrexate with radical irradiation can lead to significant improvement; and the work of the SECOG group2 and others, also with a prospectively randomised trial design, demonstrates the value of other types of chemotherapy for these disorders. He also doubts if ifosfamide has added much to cancer treatment. The combination BIP (bleomycin, ifosfamide, cisplatin) has produced impressive response rates in advanced cervical cancer,3 and MIC (mitomycin ifosfamide, cisplatin) has also led to very much higher response rates in non-small-cell lung cancer. Neither of these common cancers had previously been regarded as
responsive to chemotherapy; despite uncertainty over possible cure rates, there is no doubt about the symptomatic benefit attained in a high proportion of patients. Careful studies with adjuvant chemotherapy continue to suggest long-term benefit, possibly even cure, in patients with common solid cancers, notably breast and colorectal cancer.5.6 These advances came about only by careful study of large numbers of patients, and it is unwise of Braverman to imply that there is now less pressure to enter patients into clinical trials. Most of the important advances have been made through pooled analysis of large patient numbers; this approach has permitted the demonstration of modest statistical improvements which, because of the frequency of some of these disorders, often translates into very large numerical benefits. Department of Radiotherapy and Oncology, University College Hospital, London WC1E 6AU, UK 1.
J. S. TOBIAS
Gupta NK, Pointon RCS, Wilkinson PM. A randomized clinical trial to contrast radiotherapy with radiotherapy and methotrexate given synchronously in head and
neck cancer. Clin Radiol 1987; 38: 575-81 2. SECOG Participants. A randomized trial of combined multi-drug chemotherapy and radiotherapy in advanced squamous cell carcinoma of the head and neck. Eur J Surg Oncol 1986, 12: 289-95 3. Buxton EJ, Meanwell CA, Mould JJ, et al. Phase II studies of bleomycin, ifosfamide and cisplatinum in advanced and recurrent cervical carcinoma. Acta Oncol 1988; 27: 545-49. 4. Currie DC, Miles DW, Drake JS, et al. Mitomycin, ifosfamide and cisplatin in non-small cell lung cancer. Cancer Chemother Pharmacol 1990; 25: 380-81.
5.
Early Breast Cancer Trialists’ Collaborative Group. Treatment of early breast cancer vol I, worldwide evidence, 1985-1990. Oxford: Oxford University Press, 1990. 6. Krook JE, Moertel CG, Gunderson LL, et al. Effective surgical adjuvant therapy for high risk rectal carcinoma N Engl J Med 1991; 324: 709-15.
SIR,-Dr Braverman’s comments reach the core of how many of feel in relation to the excessive and unrewarding chemical manipulations that many cancer patients undergo in the last months of life. This often unwarranted "heroic" intervention fails to relieve discomfort or prolong life or increase its quality. I would like to believe that this aggressive approach is generated by a misguided sense of doing something, but financial considerations for the physician may sometimes be, if not a conscious, then at least a subliminal factor. The call for more restraint and discrimination in the use of chemotherapy might help to alleviate the distress of many terminally ill patients and reduce the exorbitant medical costs of their illnesses. The proper way to administer chemotherapy should be in ambulatory settings of medical institutions, rather than in doctors’ private offices. In this way the oncologist’s decisionmaking processes would be less clouded by extraneous influences. us
1735 York Avenue, New York, NY 10128, USA
JORGE A. LOPEZ-OVEJERO
SIR,-Dr Braverman highlights differences in oncological practice between the UK and the USA. America has many more medical oncologists per head of population than Britain and there is great pressure to treat all cancer patients with cytotoxic drugs, even when the chance of remission is slight. This pressure is not only financial but also generated by patients who may feel that their cancer has been inadequately treated without such treatment and who will "shop around" until they are given the treatment they think is required. In the UK the pressure to treat is much less and physicians trained in cancer medicine have already adopted most of Braverman’s recommendations. For those patients with tumours that are unlikely to benefit from cytotoxic drugs (eg, carcinoma of the pancreas and melanoma) chemotherapy is not routinely offered and these patients are either treated symptomatically or entered on research protocols investigating novel agents or biological therapies. Although, as Braverman states, etoposide is the last new drug that has had an impact on patient survival, others such as carboplatin have allowed patients to be treated with much reduced toxicity but no loss of therapeutic effect. It is therefore important to continue to investigate both new agents and analogues of existing drugs, besides biological therapies and molecules directed against other cellular targets revealed by the molecular biologists. Cancer treatment in the UK may not suffer from many of the excesses of the North American experience but the situation is far from ideal. Medical oncology is almost exclusively confined to academic teaching centres, and the oncology opinion in most district general hospitals is provided by the visiting radiotherapist who may have a weekly or fortnightly clinic. Thus, most cancer patients in the UK have limited access to specialist advice and are more likely to be denied effective therapy than to be overtreated. A better way to organise cancer services would be to have a cancer specialist in every district hospital, both to provide a local specialist service and to act as a focus for establishing hospice services and the psychological, dietary, counselling, and other support that many cancer patients require but which are so often lacking. Braverman’s comments may be pertinent to the USA, where they probably have too many cancer specialists-but they do not apply in the UK, where we certainly have too few. Department of Medical Oncology, CRC Laboratories, Charing Cross Hospital, London W6 8RF, UK
DAVID B. SMITH
SIR,-In general I agree with Dr Braverman’s severe assessment cancer chemotherapy. The cancer chemotherapist gives chemotherapy; the medical oncologist should know when not to give it. However, he does not provide the clinical oncologist with any guidance about the patient who insists on chemotherapy and will not accept hospice care. When we do not respond, such patients
of current
high level of seropositivity (6/58) was observed among Anonymous testing of more of the low-risk women in the second phase would have provided valuable information, since confirmation of the high observed seroprevalence rate (12-5%) would have important consequences for the sensitivity of a voluntary screening policy.
phase,
a
women who declined to be HIV tested.
Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, London WC1 E 7HT, UK
DAVID DUNN RICHARD HAYES
SIR,-Several UK hospitals are doing epidemiological studies, under the aegis of the Central Public Health Laboratory, Colindale, to find out the incidence of HIV infection in pregnant women. The testing is anonymous, and the only information recorded about the women is their racial origin. At St George’s Hospital, London, we book about 3500 women a year in the antenatal clinic (deliveries in 1990 were 3156). In the past fourteen months, we have tested blood samples from 4070 clinic attenders. 11were seropositive to HIV by the Abbott recombinant HIV-l/HIV-2 enzyme immunoassay. These positive tests were confirmed by the Central Public Health Laboratory. 2 other samples positive in our laboratory have not yet been checked. If they too are confirmed the seroprevalence rate will be 0-32%. We also have a high prevalence of hepatitis B carriage in our women (0-7%) and the data on HIV positivity accord with this. The seroprevalence rates are similar to those published by Heath et al from St Bartholomew’s Hospital in 1988.1 In 1987, we tested some 3000 antenatal women under the same conditions and found not 1 HIV seropositive. Thus, a substantial number of women booking at our clinics are seropositive to HIV. We also offer HIV testing on request and about 60 pregnant women were so tested in 1990, all being counselled before blood was taken. Only 2 were positive: on the assumption that these 2 were in the anonymous testing group, also, that would yield 11 other HIV-seropositive women about whom we did not know. These data have implications for the management of labour and post-partum care of mother and baby. Precautions against accidental infection of staff need to be tightened. We plan to increase the opportunities for women to be tested openly, but that means the provision of more counsellors in the antenatal clinics and increased resources in the virology laboratory. GEOFFREY CHAMBERLAIN
Departments of Obstetrics and Medical Microbiology, St George’s Hospital, London SW17 0RE, UK
JAMES BOOTH KEHINDE OMISAKIN HAROLD STERN
1. Heath RB, Grint PC, Hardiman AE. Anonymous testing of women attending antenatal clmics for evidence of infection with HIV. Lancet 1988; i: 1394.
SIR,-Dr Barbacci and colleagues argue in support of HIV antibody testing as a part of routine antenatal care. Such testing is already widespread, though in most areas it is of doubtful cost-benefit. As testing becomes more routine the associated counselling is likely to become truncated or non-existent. In my view Barbacci’s data can be interpreted as showing lack of value in extending HIV antibody testing to all women attending for antenatal care. Barbacci et al report that in Baltimore in the period before November, 1988, HIV antenatal screening, if restricted to women with a history of HIV risk, would have identified only 57% of HIV-seropositive women. Because testing was also made available to women without risk factors who wished to be tested, their programme in fact identified 83% of the HIV-positive women. (The remaining 17% were revealed by anonymous screening.) About one-third of women registering for antenatal care had a voluntary test for HIV. In November, 1988, a system which could be described as routine HIV antenatal testing was introduced; the number of voluntary HIV antibody tests increased to 76% and the proportion of all infected women who were identified in the voluntary programme rose to 87%. This increase in the yield of the voluntary programme (from 83% to 87%) was not significant. From November, 1988, among the women without risk factors
who declined testing a greater proportion were HIV positive than had been so earlier (6 out of 321 declining testing in the earlier period compared with 5 out of 40 in the later one). This decline in acceptance of HIV screening by women denying risk factors is significant (p<0001, X2). Perhaps women at risk in the earlier period had been prepared to accept testing though denying their risk status. The perceived hint of compulsion inherent in the later programme may have made such women more concerned about the consequences of a positive result. Either way in the high-risk Baltimore population, in which 4% of women are HIV positive, a sufficiently large number of HIV-positive women without risk factors will ask for HIV testing when this is not routine, so that the expansion of the programme does not appreciably increase the number of women testing positive. What is most important is the finding that a restriction of a programme to women with an identifiable risk factor, without extending it to other women requesting testing, would seriously underestimate the number of HIV-positive women. Fortunately, it is not the usual practice in which a truly voluntary programme is in place, for HIV testing not to be offered to any woman requesting it. It would be unfortunate ifBarbacci and colleagues’ interpretation that antenatal testing should be routine were to be extended from their high-risk population to low-risk populations such as most women in non-urban United States and women in Australia. Department of Immunology/Allergy, Prince of Wales Children’s Hospital,
JOHN B. ZIEGLER
Randwick, NSW 2031, Australia
Thrombotic thrombocytopenic purpura and
ticlopidine and
SIR,-Dr Page colleagues report (March 30, p 774) thrombotic thrombocytopenic purpura (TTP) after treatment with ticlopidine. Their finding contrasts with our experience1 and that of others2.3 that ticlopidine is beneficial in the treatment of TTP. We have seen two patients who after reaching complete remission with high-dose ticlopidine (750 mg daily) have been maintained at 250-500 mg daily for 38 and over 39 months, respectively, without relapse. It is difficult to explain the development of TTP after ticlodipine, which is known for its potent and unusual antiaggregating effect. TTP is usually a disease of the young adult, most commonly arising between age 30 and 40; curiously, three of Page and colleagues’ four patients were over 70. Perhaps these patients’ older age associated with impaired vascular conditions may have played a part in the pathophysiology of ticlopidine-associated TTP. We believe that these conflicting data are too few for the conclusion to be drawn that ticlopidine should not be used in patients with TTP.
Institute of Haematology "L. e A. Seràgnoli", Policlinico S Orsola, 40138 Bologna, Italy
NICOLA VIANELLI GIUSEPPE BANDINI LUCIA CATANI MONICA MATTIOLI BELMONTE LUIGI GUGLIOTTA
L, Mattioli Belmonte M, et al. Ticlopidine in the treatment of thrombotic thrombocytopenic purpura: report of two cases. Haematologica 1990;
1. Vianelli N, Catani
75: 274-77. 2. De Pasquale A, Venturoni LF, Paterlini P, et al. Possible usefulness of ticlopidine in combined treatment of thrombotic thrombocytopenic purpura: report of one case. Haematologica 1986; 71: 53-55. 3. Ishii Y, Ebata H, Satoh K. A case of thrombotic thrombocytopenic purpura, successful treatment by ticlopidine. Clin Hematol 1984; 25: 1097-102.
Ketanserin for hypertension after upper
gastrointestinal surgery SIR,-Dr Mikulic and colleagues (April 20, p 976) demonstrate
efficacy of ketanserin in the treatment of hypertension after gastrointestinal surgery. I disagree with their statement that the hypotensive action of ketanserin is attributable to its ability to act as an antagonist at peripheral postsynaptic serotonin (5-HT2) receptors. Ketanserin is not a specific antagonist at the 5-HTz the
1220
receptor, having a substantial affinity for both the ott-adrenoceptor and the histamine Hi receptor. The mechanism of the hypotension evoked by ketanserin and other 5-HT2 antagonists has been investigated by several workers,2,3 and the consensus of opinion is that the fall in blood pressure results from the ability of ketanserin to block oti-adrenoceptors within the central nervous system rather than its ability to block 5-HT2 receptors. Furthermore, the cardiovascular profile of ketanserin (ie, absence of reflex tachycardia and decrease in sympathetic nerve activity) is a feature of o-adrenoceptor antagonists such as prazosin and indoramin.4 Thus, ketanserin probably acts via the blockade of o-adrenoceptors, making prazosin and other antagonists of this site useful in the management of this particular form of hypertension. Section of Vascular Biology, MRC Clinical Research Centre, Harrow Middlesex HA1 3UJ, UK 1.
RICHARD G. BOGLE
Leysen JE, Awouters F, Kennis L, Lauduron PM, Vandenberg J, Janssen PAJ. Receptor binding profile of R41468, a novel antagonist at 5 HT2. Life Sci 1981; 28:
1015-22. JR. Mechanism of the hypotensive effect of ketanserin. J Cardiovasc Pharmacol 1982; 4: 829-38. 3. Ramage AG. Examination of the effects of some 5-HT2 antagonists on central sympathetic outflow and blood pressure in anaesthetised cats. NaunynSchmiedeberg’s Arch Pharmacol 1988, 338: 601-07 4. Ramage AG. The effect of prazosin, indoramin and phentolamine on sympathetic nerve activity. Eur J Pharmacol 1984; 106: 507-13. 2. Fozard
Medical
oncology in the 1990s
SIR,-Although I share some of Dr Braverman’s reservations (April 13, p 901) about the current role of cytotoxic chemotherapy for cancer, he paints an inaccurate picture. May I highlight one or two areas in which current research argues strongly against his nihilistic viewpoint. Braverman claims that "The apparent chemosensitivity of head and neck tumours is not reflected in survival benefits". Although the issue is far from settled, a prospective randomised study from the UKl has shown that the simple combination of methotrexate with radical irradiation can lead to significant improvement; and the work of the SECOG group2 and others, also with a prospectively randomised trial design, demonstrates the value of other types of chemotherapy for these disorders. He also doubts if ifosfamide has added much to cancer treatment. The combination BIP (bleomycin, ifosfamide, cisplatin) has produced impressive response rates in advanced cervical cancer,3 and MIC (mitomycin ifosfamide, cisplatin) has also led to very much higher response rates in non-small-cell lung cancer. Neither of these common cancers had previously been regarded as
responsive to chemotherapy; despite uncertainty over possible cure rates, there is no doubt about the symptomatic benefit attained in a high proportion of patients. Careful studies with adjuvant chemotherapy continue to suggest long-term benefit, possibly even cure, in patients with common solid cancers, notably breast and colorectal cancer.5.6 These advances came about only by careful study of large numbers of patients, and it is unwise of Braverman to imply that there is now less pressure to enter patients into clinical trials. Most of the important advances have been made through pooled analysis of large patient numbers; this approach has permitted the demonstration of modest statistical improvements which, because of the frequency of some of these disorders, often translates into very large numerical benefits. Department of Radiotherapy and Oncology, University College Hospital, London WC1E 6AU, UK 1.
J. S. TOBIAS
Gupta NK, Pointon RCS, Wilkinson PM. A randomized clinical trial to contrast radiotherapy with radiotherapy and methotrexate given synchronously in head and
neck cancer. Clin Radiol 1987; 38: 575-81 2. SECOG Participants. A randomized trial of combined multi-drug chemotherapy and radiotherapy in advanced squamous cell carcinoma of the head and neck. Eur J Surg Oncol 1986, 12: 289-95 3. Buxton EJ, Meanwell CA, Mould JJ, et al. Phase II studies of bleomycin, ifosfamide and cisplatinum in advanced and recurrent cervical carcinoma. Acta Oncol 1988; 27: 545-49. 4. Currie DC, Miles DW, Drake JS, et al. Mitomycin, ifosfamide and cisplatin in non-small cell lung cancer. Cancer Chemother Pharmacol 1990; 25: 380-81.
5.
Early Breast Cancer Trialists’ Collaborative Group. Treatment of early breast cancer vol I, worldwide evidence, 1985-1990. Oxford: Oxford University Press, 1990. 6. Krook JE, Moertel CG, Gunderson LL, et al. Effective surgical adjuvant therapy for high risk rectal carcinoma N Engl J Med 1991; 324: 709-15.
SIR,-Dr Braverman’s comments reach the core of how many of feel in relation to the excessive and unrewarding chemical manipulations that many cancer patients undergo in the last months of life. This often unwarranted "heroic" intervention fails to relieve discomfort or prolong life or increase its quality. I would like to believe that this aggressive approach is generated by a misguided sense of doing something, but financial considerations for the physician may sometimes be, if not a conscious, then at least a subliminal factor. The call for more restraint and discrimination in the use of chemotherapy might help to alleviate the distress of many terminally ill patients and reduce the exorbitant medical costs of their illnesses. The proper way to administer chemotherapy should be in ambulatory settings of medical institutions, rather than in doctors’ private offices. In this way the oncologist’s decisionmaking processes would be less clouded by extraneous influences. us
1735 York Avenue, New York, NY 10128, USA
JORGE A. LOPEZ-OVEJERO
SIR,-Dr Braverman highlights differences in oncological practice between the UK and the USA. America has many more medical oncologists per head of population than Britain and there is great pressure to treat all cancer patients with cytotoxic drugs, even when the chance of remission is slight. This pressure is not only financial but also generated by patients who may feel that their cancer has been inadequately treated without such treatment and who will "shop around" until they are given the treatment they think is required. In the UK the pressure to treat is much less and physicians trained in cancer medicine have already adopted most of Braverman’s recommendations. For those patients with tumours that are unlikely to benefit from cytotoxic drugs (eg, carcinoma of the pancreas and melanoma) chemotherapy is not routinely offered and these patients are either treated symptomatically or entered on research protocols investigating novel agents or biological therapies. Although, as Braverman states, etoposide is the last new drug that has had an impact on patient survival, others such as carboplatin have allowed patients to be treated with much reduced toxicity but no loss of therapeutic effect. It is therefore important to continue to investigate both new agents and analogues of existing drugs, besides biological therapies and molecules directed against other cellular targets revealed by the molecular biologists. Cancer treatment in the UK may not suffer from many of the excesses of the North American experience but the situation is far from ideal. Medical oncology is almost exclusively confined to academic teaching centres, and the oncology opinion in most district general hospitals is provided by the visiting radiotherapist who may have a weekly or fortnightly clinic. Thus, most cancer patients in the UK have limited access to specialist advice and are more likely to be denied effective therapy than to be overtreated. A better way to organise cancer services would be to have a cancer specialist in every district hospital, both to provide a local specialist service and to act as a focus for establishing hospice services and the psychological, dietary, counselling, and other support that many cancer patients require but which are so often lacking. Braverman’s comments may be pertinent to the USA, where they probably have too many cancer specialists-but they do not apply in the UK, where we certainly have too few. Department of Medical Oncology, CRC Laboratories, Charing Cross Hospital, London W6 8RF, UK
DAVID B. SMITH
SIR,-In general I agree with Dr Braverman’s severe assessment cancer chemotherapy. The cancer chemotherapist gives chemotherapy; the medical oncologist should know when not to give it. However, he does not provide the clinical oncologist with any guidance about the patient who insists on chemotherapy and will not accept hospice care. When we do not respond, such patients
of current