540
resistance was also reported, with a negative effect on H pylori eradication.4 This finding might affect the choice of treatment in an MTZ-resistant patient. To quantify MTZ resistance pretreatment and to establish factors that might be implicated we investigated 140 consecutive patients with peptic ulcer disease or non-ulcer dyspepsia. H pylori was cultured from gastric mucosal biopsy specimens, and in-vitro sensitivity to MTZ before treatment was tested with a disc diffusion method. Nine isolates (6-4%) were MTZ resistant: of 91 H pyloripositive men only 2 (2-2%) were MTZ resistant, whereas 7 of 49 women had such resistance (14-3%, p < 0-02). MTZ is used for vaginal infections (gardnerella, trichomonas), for amoebiasis, and as a perioperative prophylaxis in uterine and colonic surgery. Factors that might have caused MTZ resistance were checked in the 9 patients (mean age 47-8 years, range 33-67) with MTZ-resistant H pylori, and in a subgroup of 18 patients with MTZ-sensitive H pylori, matched for sex and age. Previous use of MTZ was indicated in 7 of 9 patients with MTZ-resistant H pylori : 2 women had been treated for vaginal infections and 1 man for giardiasis; 4 women had had hysterectomies in the past 5 years. In the MTZ-sensitive group only 2 of 18 patients had a history of (probable) use of MTZ (p < 0-005) (2 women had had uterine surgery). None of the patients in either group had had surgery of the colon. The frequency of H pylori resistance to MTZ before treatment in our population is very low in men, but is considerable in women. Its occurrence is associated with previous use of MTZ for other reasons, which can usually be established from the patient’s history. The use of MTZ in treatment schedules for eradication of H pylori will probably increase MTZ resistance. In vitro testing of H pylori sensitivity to MTZ seems to be important. Departments of Internal Medicine and Bacteriology, Canisius-Wilhelmina Hospital, 6500 GS Nijmegen, Netherlands
M. C. J. M. BECX A. J. H. M. JANSSEN H. A. L.CLASENER R. W. DE KONING
Langenberg W, Houthoff HJ, Zanen HC, Tytgat GNJ. Campylobacter pyloridis-associated chronic active gastritis. Gastroenterology 1988; 94: 33-40. 2. Andreasen JJ, Andersen LP. In vitro susceptibility of Campylobacter pylori to 1. Rauws EAJ,
cimetidine, sucralfate, bismuth and sixteen antibiotics. Acta Path Microbiol Immunol Scand (Sect B) 1987; 95: 147-49. 3. Marshall BJ, Goodwin CS, Warren JR, et al. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet 1988; ii: 1437-42. 4. Goodwin CS, Marshall BJ, Blincow ED, Wilson DH, Blackbourn S, Phillips M. Prevention of nitroimidazole resistance in Campylobacter pylori by coadministration of bismuth subcitrate: clinical and in vitro studies. J Clin Pathol 1988; 41: 207-10. 5. Glupczynski Y, Labbe M, Burette A, Delmee M, Avesani V, Bruck C. Treatment failure of ofloxacin in Campylobacter pylori infection. Lancet 1987; i: 1096.
Measles vaccination in early infancy SIR,-Dr Tidjani and colleagues (Dec 9, p 1357) report successful measles vaccination of children aged 4-5 months living in Lome (Togo). Seroconversion rates were 94% with the EdmonstonZagreb (EZ) vaccine strain and96% with the AIK-C strain but only 50% with the Schwarz vaccine strain. The efficacy of the EZ strain is not unexpected. Whittle et al,l reported from the Gambia only 1 seronegative, out of 113 children vaccinated at age 4 months, on follow-up 5 months after vaccination; and by the age of 18 months the antibody titre had doubled, presumably due to contact with children with natural measles. This pattern seems characteristic of a hyperendemic area where the chance of contact with circulating wild virus is very high. In Switzerland a comparative trial has been done with medium dose EZ vaccine (Berna;1045 PFU/103-5 TCIDso) and Schwarz vaccine (SK Biologicals; lOS-11 PFU/108 TCIDso) in children aged 4-8-75 months (mean 59). Blood was taken on the day of vaccination, 40 days later, and at the age of 14-17 months at the time of routine MMR vaccination and, on average, 9-5 months after measles immunisation. Measles antibodies were assayed by haemagglutination inhibition (HAI) and plaque neutralisation
(PN).
44/103 children were seropositive on the day of vaccination, due maternal antibody. At 40 days the initially seronegative children showed seroconversion rates of 92% (HAI) and 91 % (PN) for the EZ vaccine and 100% (HAI and PN) for the Schwarz vaccine. Children with maternal antibody on the day of vaccination had seropositivity rates of 97% (HAI) and 100% (PN) for the EZ and 100% (HAI and PN) for the Schwarz strains. At 14-17 months all initial seronegatives had measles antibodies detectable by PN (geometric mean titre 1265 mIU/ml for EZ and 2107 mIU/ml for Schwarz vaccine). The HAI test detected measles antibody in 86% of the children vaccinated with the EZ and 80% given the Schwarz
to
strain. The initially seropositive vaccinees showed a remarkable difference in persistence of immunity. 70% of children vaccinated with the EZ strain had antibodies detectable by the PN test and 63% by HAI. The lower efficacy of the Schwarz strain reported by Tidjani, Whittle, and many others was confirmed. Only 42% of children vaccinated with Schwarz vaccine had measles antibodies by PN test and 0% by HAI. In contrast to the epidemiological situation in Africa, natural measles infection below the age of 15-18 months, the age when routine MMR vaccination is recommended, is very uncommon in Switzerland. 2 out of 220 and none of 150 children tested in 1985 and 1986 had a previous measles infection at that age. Long-term immunity induced by EZ vaccination was therefore not affected by natural measles infection or booster and a change to earlier age for measles immunisation in Switzerland has not been recommended. In Tidjani’s study 13% of the children with two prevaccination assays were infected by measles at 6-7 to 8-10 months and 25% of children vaccinated at age 4-5 months and still seronegative at the first post-vaccination check had been infected between 6-7 and 10-12 months. Despite the high probability of infection 56% of the initially seropositive children vaccinated with EZ strain, 50% of those vaccinated with the AIK-C strain, and only 12% vaccinated with the Schwarz strain were protected at the age of 1 year. This protection was even lower than it was in the Swiss study, were 70% of initially seropositives vaccinated with the EZ strain had antibodies at age 15 months. Bearing in mind the number of primary and booster infections by circulating wild virus1 the results with even high-dose immunisation in seropositive childen in the hyperendemic situation in Lome were far from expected. Another explanation could be that the HAI test used by Tidjani et al failed to detect a low-positive antibody titre. Whatever the explanation, it seems that measles vaccination in early infancy is not the final answer even if more efficient vaccine strains were to become available. Improvements in the epidemiological situation brought about by expanded immunisation programmes may result in a shift of measles infection to older ages and in successful vaccination for all children at a more appropriate age.
ROSEMARIE BERGER MAX JUST REINHARD GLÜCK MANUELA GRASSI ALFRED WEGMANN
University Children’s Hospital, 4005 Basel, Switzerland, and Swiss Serum and Vaccine Institute, Bern 1. Whittle H, Hanlon P, O’Neill K, et al. Trial of
high-dose Edmonston-Zagreb measles 1988, ii: 811-14
vaccine in the Gambia: antibody response and side-effects. Lancet
Side-effects of measles-mumps vaccination SIR,-In the continuing debatel on the side-effects of mumps vaccination, I would raise two issues: the frequency of adverse effects and vaccination-induced
idiopathic thrombocytopenia
(ITP). Dr Nalin (Dec 9, p 1396) refers to five culture-proven cases of post-vaccination mumps meningitis in West Germany, citing my review.2 I have seen only one patient2,3 and no further cases have been reported from Germany. However, because of our very poor reporting of pharmacological side-effects, estimations resulting from reports to the manufacturer in our country can be misleading, and frequency estimations should not be based on these reports.
541
Thus, in the Kinderhospital Osnabriick alone (serving a population of 450 000), we have seen over four years 3 cases of measles-mumps vaccination (MM-V) induced parotitis, 1 of meningitis, 1 of immune thrombocytopenic purpura (ITP), and 1 post-vaccination death. We reported these cases to the appropriate authorities and to the manufacturers. The patient who died was a severely mentally retarded 16-month-old girl, and death occurred 20 days after vaccination (Moraten/Jeryl-Lynn). She had central respiratory and vasomotor failure and cerebrospinal fluid protein of 973 mg/dl, but raised cell count. These findings indicate that the true frequency may be much higher than estimated from manufacturers’ records. Severe ITP was noted in a 19-month-old girl 11days after MM-V (Schwarz/Urabe). Her platelet count was 5800/J.Ù. She did not respond to immunoglobulins, but made a prompt and complete recovery after prednisone 2 We have since seen another patient, a no
16-month-old girl, with ITP (platelet count 32 000/)il) on the 22nd day after MM-V (Moraten/Jeryl-Lynn). She recovered promptly after immunoglobulin. ITP is probably a non-specific side-effect of vaccination; but in counselling of parents on the possibility of meningitis,! the far greater probability of ITP should also be included. Kinderhospital, Iburger Str 187, 4500 Osnabruck, FRG
K. E. VON MÜHLENDAHL
1. Editorial. Mumps meningitis and MMR vaccination. Lancet 1989; ii: 1015-16. 2. Von Mühlendahl KE. Nebenwirkungen und Komplikationen der Masern-MumpsImpfung. Monatsschr Kinderheilk 1989; 1137: 440-46. 3. Von Mühlendahl KE. Mumps meningitis following measles, mumps, and rubella immunisation. Lancet 1989; ii: 394.
Adjuvant tamoxifen in postmenopausal stage II breast cancer five years on SiR,—Combined adjuvant treatment with tamoxifen (20 mg daily plus cyclophosphamide, methotrexate, and fluorouracil (CMF)1 has been investigated in a prospective randomised study. 322 patients (233 postmenopausal) with breast cancer were recruited between 1980 and 1985. We report here on the results in 100 postmenopausal patients with stage II disease. After modified radical mastectomy they were randomised to receive daily tamoxifen (n = 33), six cycles of CMF (n = 35), or both (n = 32), beginning 2-4 weeks after surgery. Stratification criteria included oestrogen receptor content of the tumour,2 number of axillary lymph nodes affected, and histological grading. Follow-up to an average of 48 months3 pointed to an advantage in disease-free interval (DFI) for combined adjuvant treatment. However, analysis in the same patients after a mean observation period of 60 months revealed a clear-cut advantage for tamoxifen alone (50% of patients disease-free) over both tamoxifen plus CMF (44%) and CMF (37%) (fig 1). The 5-year-survival rates were 76% in the group receiving tamoxifen, 61 % in the group receiving CMF, and 65% in the group receiving combined therapy (fig 2). Histological grading and number of affected lymph nodes were important predictors: patients with grade 3 tumours had a survival of 48% whereas the patients with the worst prognosis were those with tumours of grade 3 plus more than six affected lymph nodes
(19%). Our data show that combined adjuvant treatment with tamoxifen to only a preliminary increase in disease-free
plus CMF leads
Fig 2-Survival. survival which does not persist up to 5 years after the breast surgery. and number of involved axillary lymph nodes taken together constitute an important prognostic index in breast cancer and should be taken into account in the planning of future studies.
Histological grade
P. AIGINGER K. CZERWENKA E. KUBISTA H. SALZER P. SEVELDA A. STAFFEN J. SPONA C. C. ZIELINSKI
J. MIKL Departments of Medicine II, Obstetrics and Gynaecology, and Surgery II, University Hospital, A-1090, Vienna, Austria
G, Rossi A, Valagussa P. Adjuvant chemotherapy in operable breast years later. Lancet 1985; i: 976-77. 2. Zielinski CC, Tichatschek E, Muller C, et al. Association of increased lyric effector cell function with high estrogen receptor levels in tumour-bearing patients with breast 1. Bonadonna
cancer: ten
cancer. Cancer 1989; 63: 113-17. 3. Zielinski CC, Kubista E, Salzer H, et al. Adjuvant chemotherapy combined with tamoxifen in postmenopausal patients with stage II breast cancer. Lancet 1986; ii: 1164.
Vomiting and chemotherapy SiR,—Your Feb 3 editorial highlights a serious clinical problem. In survey of 204 patients treated over 4 months, we found some degree of sickness in 77%, the frequency for those on cisplatin being 97%. In 60% sickness was severe and prolonged. In addition to the drugs you mention we recommend consideration of intravenous cyclizine and rectal thiethylperazine. Another useful adjuvant to standard antiemetics is P6 acupuncture. In 105 patients who had had troublesome sickness during a previous course of treatment despite the use of antiemetics, 99 benefited from acupuncture before cisplatin,l with 63% having complete relief of
a
symptoms. Italian workers report similar results? As in single doses of most antiemetics the beneficial effects of acupuncture last only for 8 hours. However, the use of acupressure over P6, with the commercially available ’Sea Bands’, can prolong this action with 24 h. The band is applied on the dominant side with instructions to press the stud for 5 min every 2 h.3 However, acupuncture is time consuming and requires technical skill. Workers have lately shown that transcutaneous electrical stimulation over the P6 point will produce results almost as good as those for acupuncture. We now use large surface electrodes in combination with a simple ’Mini-tens’ stimulator (15 Hz for 5 min). The stimulus can be applied by the patient every 2 h, and this patient participation in treatment seems to be important. This technique could be a useful simple non-toxic adjuvant to standard antiemetics. Northern Ireland Centre for Radiotherapy and Oncology, Belvoir Park Hospital, UK Belfast BT8 &JR,
JOHN W. DUNDEE JING YANG R. GEORGE GHALY
1. Dundee
JW, Ghaly RG, Fitzpatrick KTJ, Abram WP, Lynch GA. Acupuncture prophylaxis of cancer chemotherapy-induced sickness. R Soc Med 1989; 82: 268-71.
Agliette L. A pilot study of metoclopramide, dexamethasone, diphenhydramine and acupuncture in female patients treated with cisplatin. Cancer Chemother Pharmacol (in press). 3. Dundee JW, Yang J. Acupressure prolongs the anti-emetic action of P6 acupuncture. Br J Clin Pharmacol (in press).
2.
Fig 1-Disease freedom.
resistance was also reported, with a negative effect on H pylori eradication.4 This finding might affect the choice of treatment in an MTZ-resistant patient. To quantify MTZ resistance pretreatment and to establish factors that might be implicated we investigated 140 consecutive patients with peptic ulcer disease or non-ulcer dyspepsia. H pylori was cultured from gastric mucosal biopsy specimens, and in-vitro sensitivity to MTZ before treatment was tested with a disc diffusion method. Nine isolates (6-4%) were MTZ resistant: of 91 H pyloripositive men only 2 (2-2%) were MTZ resistant, whereas 7 of 49 women had such resistance (14-3%, p < 0-02). MTZ is used for vaginal infections (gardnerella, trichomonas), for amoebiasis, and as a perioperative prophylaxis in uterine and colonic surgery. Factors that might have caused MTZ resistance were checked in the 9 patients (mean age 47-8 years, range 33-67) with MTZ-resistant H pylori, and in a subgroup of 18 patients with MTZ-sensitive H pylori, matched for sex and age. Previous use of MTZ was indicated in 7 of 9 patients with MTZ-resistant H pylori : 2 women had been treated for vaginal infections and 1 man for giardiasis; 4 women had had hysterectomies in the past 5 years. In the MTZ-sensitive group only 2 of 18 patients had a history of (probable) use of MTZ (p < 0-005) (2 women had had uterine surgery). None of the patients in either group had had surgery of the colon. The frequency of H pylori resistance to MTZ before treatment in our population is very low in men, but is considerable in women. Its occurrence is associated with previous use of MTZ for other reasons, which can usually be established from the patient’s history. The use of MTZ in treatment schedules for eradication of H pylori will probably increase MTZ resistance. In vitro testing of H pylori sensitivity to MTZ seems to be important. Departments of Internal Medicine and Bacteriology, Canisius-Wilhelmina Hospital, 6500 GS Nijmegen, Netherlands
M. C. J. M. BECX A. J. H. M. JANSSEN H. A. L.CLASENER R. W. DE KONING
Langenberg W, Houthoff HJ, Zanen HC, Tytgat GNJ. Campylobacter pyloridis-associated chronic active gastritis. Gastroenterology 1988; 94: 33-40. 2. Andreasen JJ, Andersen LP. In vitro susceptibility of Campylobacter pylori to 1. Rauws EAJ,
cimetidine, sucralfate, bismuth and sixteen antibiotics. Acta Path Microbiol Immunol Scand (Sect B) 1987; 95: 147-49. 3. Marshall BJ, Goodwin CS, Warren JR, et al. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet 1988; ii: 1437-42. 4. Goodwin CS, Marshall BJ, Blincow ED, Wilson DH, Blackbourn S, Phillips M. Prevention of nitroimidazole resistance in Campylobacter pylori by coadministration of bismuth subcitrate: clinical and in vitro studies. J Clin Pathol 1988; 41: 207-10. 5. Glupczynski Y, Labbe M, Burette A, Delmee M, Avesani V, Bruck C. Treatment failure of ofloxacin in Campylobacter pylori infection. Lancet 1987; i: 1096.
Measles vaccination in early infancy SIR,-Dr Tidjani and colleagues (Dec 9, p 1357) report successful measles vaccination of children aged 4-5 months living in Lome (Togo). Seroconversion rates were 94% with the EdmonstonZagreb (EZ) vaccine strain and96% with the AIK-C strain but only 50% with the Schwarz vaccine strain. The efficacy of the EZ strain is not unexpected. Whittle et al,l reported from the Gambia only 1 seronegative, out of 113 children vaccinated at age 4 months, on follow-up 5 months after vaccination; and by the age of 18 months the antibody titre had doubled, presumably due to contact with children with natural measles. This pattern seems characteristic of a hyperendemic area where the chance of contact with circulating wild virus is very high. In Switzerland a comparative trial has been done with medium dose EZ vaccine (Berna;1045 PFU/103-5 TCIDso) and Schwarz vaccine (SK Biologicals; lOS-11 PFU/108 TCIDso) in children aged 4-8-75 months (mean 59). Blood was taken on the day of vaccination, 40 days later, and at the age of 14-17 months at the time of routine MMR vaccination and, on average, 9-5 months after measles immunisation. Measles antibodies were assayed by haemagglutination inhibition (HAI) and plaque neutralisation
(PN).
44/103 children were seropositive on the day of vaccination, due maternal antibody. At 40 days the initially seronegative children showed seroconversion rates of 92% (HAI) and 91 % (PN) for the EZ vaccine and 100% (HAI and PN) for the Schwarz vaccine. Children with maternal antibody on the day of vaccination had seropositivity rates of 97% (HAI) and 100% (PN) for the EZ and 100% (HAI and PN) for the Schwarz strains. At 14-17 months all initial seronegatives had measles antibodies detectable by PN (geometric mean titre 1265 mIU/ml for EZ and 2107 mIU/ml for Schwarz vaccine). The HAI test detected measles antibody in 86% of the children vaccinated with the EZ and 80% given the Schwarz
to
strain. The initially seropositive vaccinees showed a remarkable difference in persistence of immunity. 70% of children vaccinated with the EZ strain had antibodies detectable by the PN test and 63% by HAI. The lower efficacy of the Schwarz strain reported by Tidjani, Whittle, and many others was confirmed. Only 42% of children vaccinated with Schwarz vaccine had measles antibodies by PN test and 0% by HAI. In contrast to the epidemiological situation in Africa, natural measles infection below the age of 15-18 months, the age when routine MMR vaccination is recommended, is very uncommon in Switzerland. 2 out of 220 and none of 150 children tested in 1985 and 1986 had a previous measles infection at that age. Long-term immunity induced by EZ vaccination was therefore not affected by natural measles infection or booster and a change to earlier age for measles immunisation in Switzerland has not been recommended. In Tidjani’s study 13% of the children with two prevaccination assays were infected by measles at 6-7 to 8-10 months and 25% of children vaccinated at age 4-5 months and still seronegative at the first post-vaccination check had been infected between 6-7 and 10-12 months. Despite the high probability of infection 56% of the initially seropositive children vaccinated with EZ strain, 50% of those vaccinated with the AIK-C strain, and only 12% vaccinated with the Schwarz strain were protected at the age of 1 year. This protection was even lower than it was in the Swiss study, were 70% of initially seropositives vaccinated with the EZ strain had antibodies at age 15 months. Bearing in mind the number of primary and booster infections by circulating wild virus1 the results with even high-dose immunisation in seropositive childen in the hyperendemic situation in Lome were far from expected. Another explanation could be that the HAI test used by Tidjani et al failed to detect a low-positive antibody titre. Whatever the explanation, it seems that measles vaccination in early infancy is not the final answer even if more efficient vaccine strains were to become available. Improvements in the epidemiological situation brought about by expanded immunisation programmes may result in a shift of measles infection to older ages and in successful vaccination for all children at a more appropriate age.
ROSEMARIE BERGER MAX JUST REINHARD GLÜCK MANUELA GRASSI ALFRED WEGMANN
University Children’s Hospital, 4005 Basel, Switzerland, and Swiss Serum and Vaccine Institute, Bern 1. Whittle H, Hanlon P, O’Neill K, et al. Trial of
high-dose Edmonston-Zagreb measles 1988, ii: 811-14
vaccine in the Gambia: antibody response and side-effects. Lancet
Side-effects of measles-mumps vaccination SIR,-In the continuing debatel on the side-effects of mumps vaccination, I would raise two issues: the frequency of adverse effects and vaccination-induced
idiopathic thrombocytopenia
(ITP). Dr Nalin (Dec 9, p 1396) refers to five culture-proven cases of post-vaccination mumps meningitis in West Germany, citing my review.2 I have seen only one patient2,3 and no further cases have been reported from Germany. However, because of our very poor reporting of pharmacological side-effects, estimations resulting from reports to the manufacturer in our country can be misleading, and frequency estimations should not be based on these reports.
541
Thus, in the Kinderhospital Osnabriick alone (serving a population of 450 000), we have seen over four years 3 cases of measles-mumps vaccination (MM-V) induced parotitis, 1 of meningitis, 1 of immune thrombocytopenic purpura (ITP), and 1 post-vaccination death. We reported these cases to the appropriate authorities and to the manufacturers. The patient who died was a severely mentally retarded 16-month-old girl, and death occurred 20 days after vaccination (Moraten/Jeryl-Lynn). She had central respiratory and vasomotor failure and cerebrospinal fluid protein of 973 mg/dl, but raised cell count. These findings indicate that the true frequency may be much higher than estimated from manufacturers’ records. Severe ITP was noted in a 19-month-old girl 11days after MM-V (Schwarz/Urabe). Her platelet count was 5800/J.Ù. She did not respond to immunoglobulins, but made a prompt and complete recovery after prednisone 2 We have since seen another patient, a no
16-month-old girl, with ITP (platelet count 32 000/)il) on the 22nd day after MM-V (Moraten/Jeryl-Lynn). She recovered promptly after immunoglobulin. ITP is probably a non-specific side-effect of vaccination; but in counselling of parents on the possibility of meningitis,! the far greater probability of ITP should also be included. Kinderhospital, Iburger Str 187, 4500 Osnabruck, FRG
K. E. VON MÜHLENDAHL
1. Editorial. Mumps meningitis and MMR vaccination. Lancet 1989; ii: 1015-16. 2. Von Mühlendahl KE. Nebenwirkungen und Komplikationen der Masern-MumpsImpfung. Monatsschr Kinderheilk 1989; 1137: 440-46. 3. Von Mühlendahl KE. Mumps meningitis following measles, mumps, and rubella immunisation. Lancet 1989; ii: 394.
Adjuvant tamoxifen in postmenopausal stage II breast cancer five years on SiR,—Combined adjuvant treatment with tamoxifen (20 mg daily plus cyclophosphamide, methotrexate, and fluorouracil (CMF)1 has been investigated in a prospective randomised study. 322 patients (233 postmenopausal) with breast cancer were recruited between 1980 and 1985. We report here on the results in 100 postmenopausal patients with stage II disease. After modified radical mastectomy they were randomised to receive daily tamoxifen (n = 33), six cycles of CMF (n = 35), or both (n = 32), beginning 2-4 weeks after surgery. Stratification criteria included oestrogen receptor content of the tumour,2 number of axillary lymph nodes affected, and histological grading. Follow-up to an average of 48 months3 pointed to an advantage in disease-free interval (DFI) for combined adjuvant treatment. However, analysis in the same patients after a mean observation period of 60 months revealed a clear-cut advantage for tamoxifen alone (50% of patients disease-free) over both tamoxifen plus CMF (44%) and CMF (37%) (fig 1). The 5-year-survival rates were 76% in the group receiving tamoxifen, 61 % in the group receiving CMF, and 65% in the group receiving combined therapy (fig 2). Histological grading and number of affected lymph nodes were important predictors: patients with grade 3 tumours had a survival of 48% whereas the patients with the worst prognosis were those with tumours of grade 3 plus more than six affected lymph nodes
(19%). Our data show that combined adjuvant treatment with tamoxifen to only a preliminary increase in disease-free
plus CMF leads
Fig 2-Survival. survival which does not persist up to 5 years after the breast surgery. and number of involved axillary lymph nodes taken together constitute an important prognostic index in breast cancer and should be taken into account in the planning of future studies.
Histological grade
P. AIGINGER K. CZERWENKA E. KUBISTA H. SALZER P. SEVELDA A. STAFFEN J. SPONA C. C. ZIELINSKI
J. MIKL Departments of Medicine II, Obstetrics and Gynaecology, and Surgery II, University Hospital, A-1090, Vienna, Austria
G, Rossi A, Valagussa P. Adjuvant chemotherapy in operable breast years later. Lancet 1985; i: 976-77. 2. Zielinski CC, Tichatschek E, Muller C, et al. Association of increased lyric effector cell function with high estrogen receptor levels in tumour-bearing patients with breast 1. Bonadonna
cancer: ten
cancer. Cancer 1989; 63: 113-17. 3. Zielinski CC, Kubista E, Salzer H, et al. Adjuvant chemotherapy combined with tamoxifen in postmenopausal patients with stage II breast cancer. Lancet 1986; ii: 1164.
Vomiting and chemotherapy SiR,—Your Feb 3 editorial highlights a serious clinical problem. In survey of 204 patients treated over 4 months, we found some degree of sickness in 77%, the frequency for those on cisplatin being 97%. In 60% sickness was severe and prolonged. In addition to the drugs you mention we recommend consideration of intravenous cyclizine and rectal thiethylperazine. Another useful adjuvant to standard antiemetics is P6 acupuncture. In 105 patients who had had troublesome sickness during a previous course of treatment despite the use of antiemetics, 99 benefited from acupuncture before cisplatin,l with 63% having complete relief of
a
symptoms. Italian workers report similar results? As in single doses of most antiemetics the beneficial effects of acupuncture last only for 8 hours. However, the use of acupressure over P6, with the commercially available ’Sea Bands’, can prolong this action with 24 h. The band is applied on the dominant side with instructions to press the stud for 5 min every 2 h.3 However, acupuncture is time consuming and requires technical skill. Workers have lately shown that transcutaneous electrical stimulation over the P6 point will produce results almost as good as those for acupuncture. We now use large surface electrodes in combination with a simple ’Mini-tens’ stimulator (15 Hz for 5 min). The stimulus can be applied by the patient every 2 h, and this patient participation in treatment seems to be important. This technique could be a useful simple non-toxic adjuvant to standard antiemetics. Northern Ireland Centre for Radiotherapy and Oncology, Belvoir Park Hospital, UK Belfast BT8 &JR,
JOHN W. DUNDEE JING YANG R. GEORGE GHALY
1. Dundee
JW, Ghaly RG, Fitzpatrick KTJ, Abram WP, Lynch GA. Acupuncture prophylaxis of cancer chemotherapy-induced sickness. R Soc Med 1989; 82: 268-71.
Agliette L. A pilot study of metoclopramide, dexamethasone, diphenhydramine and acupuncture in female patients treated with cisplatin. Cancer Chemother Pharmacol (in press). 3. Dundee JW, Yang J. Acupressure prolongs the anti-emetic action of P6 acupuncture. Br J Clin Pharmacol (in press).
2.
Fig 1-Disease freedom.
