129

keeper for B. 1., and H. C. was a maid for D. L., whose close friend was A. T. Among the randomly selected clinic patients with Hodgkin’s disease, 1 girl became ill within a year of steadily dating a man with a

The data now available indicate that patients with either leukaemia or lymphoma often have had direct or indirect close personal associations with other similar patients. This finding is consistent with the hypothesis that some forms of human leukaemia and lymphoma may be associated with the transmission of some agent(s) from person to person. Major and continuing assistance was offered by Mrs Frances Shaver, Dr William L. Cook, and their associates at the West Virginia Division of Cancer Control tumour registry and by the many patients, their friends, and families who kindly allowed an intrusion into their personal lives. The comments of Dr George Comstock and Dr J. N. P. Davies are gratefully

acknowledged.

Requests

for

reprints

should be addressed to S. C. S.

REFERENCES

Rubin, H., Cornelius, A., Fanshier, L. Proc. natn. Acad. Sci. U.S.A. 1961, 47, 1058. 2. Hardy, W. D., Hess, P. W., Essex, M., Cotter, S. Nature, 1973, 244, 266. 3. Hardy, W. D., Geering, G., Old, L. S., deHarven, E., Brodey, R. S., McDonough, S. Science, 1969, 166, 1019. 4. Vianna, N. J., Greenwald, P., Davies, J. N. P. Lancet, 1971, i, 1209. 5. Vianna, N. J., Greenwald, P., Brody, J., Polan, A. K., Dwark, A., Mauro, J., Davies, J. N. P. Ann. intern. Med. 1972, 77, 169. 6. Kemmoona, I. Lancet, 1974, i, 944. 7. Reske-Nielson, E., Peterson, J. H., Sogaard, H., Jensen, K. B. ibid. p. 210. 8. Klinger, R. S., Minton, J. P. ibid. 1973, i, 168. 9. Heath, C. W., Everett, J. R., Steward, J. T., Daines, J., Daines, P. H. ibid. p. 669. 10. Levine, P. H., Sandler, S. G., Komp, D. M., O’Conor, G. T., O’Conor, D. M. New Engl. J. Med. 1973, 288, 562. 11. Gilmore, H. R., Zelesnick, G. Penn. med. J. 1962, 65, 1047. 12. Parker, J. E. Lancet, 1974, i, 210. 13. Merrington, M., Spicer, C. C. Br. J. prev. soc. Med. 1969, 23, 124. 14. Adlerson, M. R., Nayak, R. ibid. 1971, 25, 168. 15. Heath, C. W., Hasterlik, R. S. Am. J. Med. 1963, 34, 796. 16. Vianna, N. J., Polan, A. K. New Engl. J. Med. 1973, 289, 499. 17. Gross, L. Oncogenic Viruses. New York, 1970. 18. Heath, C. W., Rosenstock, J. G., Lobdell, G. Lancet, 1971, ii, 426. 19. Smith, P. G., Pike, M. C., Kinlen, L. S. ibid. 1973, i, 433. 20. Pike, M. C., Smith, P. G. Cancer, 1974, 34, 1390. 1.

J.

BERRY*

Radiotherapy Department, Churchill Hospital, Headington, Oxford OX3 7LJ C. R. NEWMAN Horton General

Hospital, Banbury, Oxon P. SMITH

rebuild his house. These instances of close personal contact between individuals with leukaemia or lymphoma cannot be lightly dismissed. Nevertheless, there is still need for proof that the associations reported among patients are more common than would be expected for individuals living in the area under investigation. We are attempting to resolve this issue in a fourth area. A group of individuals matched for age, sex, race, and home location has been selected to determine if they will or will not have the same frequency of past close social interactions as did the patient group.

R.

A. H. LAING

girl developed Hodgkin’s disease within two years of the same diagnosis in her closest friend, acute leukaemia developed in a child of a family who transiently housed a patient with Hodgkin’s disease, and Hodgkin’s disease occurred in a young man who helped a friend with Hodgkin’s disease

Hodgkin’s disease, !

TREATMENT OF SMALL-CELL CARCINOMA OF BRONCHUS

D.H.S.S. Cancer

Epidemiology Clinical Trials Unit, Oxford

A randomised trial comparing radiotherapy with a multiple chemotherapy in 68 regimen patients with small-cell carcinoma of bronchus is reported. Although overall survival was poor, radiotherapy resulted in significantly longer survival, better amelioration of symptoms, and less side-effects than chemotherapy. Patients achieving

Sum ary

complete or partial remission on radiotherapy relapsed mainly with extrathoracic disease, in contradistinction to those treated with chemotherapy whose thoracic disease recurred.

Introduction A RANDOMISED trial of the treatment of inoperable carcinoma of the bronchus was started in the Oxford

region in 1970 as a second stage to the trial reported by Durrant et al.,1 patients being entered into the trial from seven participating centres in the region. All patients presenting with carcinoma of the bronchus were eligible for entry into the trial except those patients so ill that symptomatic treatment only was indicated. This report considers one group of the trial patients, consisting of all those patients initially diagnosed as having small-cell carcinoma of the bronchus (W.H.O. classification). These tumours are known to have a different morphological characteristic, natural history, prognosis, and response to treatment to other histological types,2-’ and they have therefore been considered separately. Patients were assigned at first presentation to receive treatment with either radiotherapy or intermittent combination chemotherapy. Treatment

Radiotherapy Treatment was by supervoltage irradiation using parallel-opposed fields to the whole mediastinum. The supraclavicular region was treated in all patients by an extension to both anterior and posterior fields if glands were present, or otherwise by an extension to the anterior field only. The dose employed was 3500 rads midline in four weeks treating daily (3500 rads in 20 fractions in 25 days), or 3000 rads treating three times weekly If residual (3000 rads in 12 fractions in 25 days). present, a further 1000 rads in 1 week could given (1000 rads in 5 fractions in 4 days).

tumour was

be

Chemotherapy Treatment bination of *

was by pulsed administration of a comnitrogen mustard (mustine hydrochloride),

Present address: M.R.C.

Radiobiology Unit, Harwell, Didcot, Oxon.

130

vinblastine, procarbazine, and prednisolone. Six 14-day courses of treatment with 14-day gaps were planned, after which the period between treatments was extended to 28 days. In each course nitrogen mustard 0’15 mg. per kg. and vinblastine 0-25 mg. per kg. were administered on days 0 and 7; and procarbazine 2-5 mg. per kg. and prednisolone 40 mg. were administered daily from day 0 to 14. This particular combination of drugs was adopted because there was fair general experience throughout the Oxford region of the use of a similar though less intensive regimen in Hodgkin’s disease, and the three cytotoxic agents chosen had all been shown to exert an objective effect in small-cell carcinoma of the bronchus.8 Prednisolone was retained because of the feeling of general well-being induced by steroids and because of anecdotal evidence that it may reduce the vomiting induced by the drug combination. However, the standard Hodgkin’s regimenwas modified in the expectation that bronchial carcinoma would be more resistant to treatment than are tumours of the reticuloendothelial system. Accordingly, the interval between pulses was reduced to 2 weeks instead of 4; and the doses of vinblastine on days 0 and 7 were increased, but the third dose of vinblastine normally employed in Hodgkin’s disease was withdrawn.

u

itiu

r_vti

-JlUU

-tuli

vuu

vvv

I UU

aw

DAYS TO DEATH

Fig. I-Actuarial survival of

all trial patients with small-cell carcinoma of bronchus.

or degree of limitation in his activity. After degree to which symptoms had been controlled was recorded, as well as an assessment of whether treatment had played a part in causing death.

symptoms death the

Assessment is unlikely and prolonged survival the exception, survival-rates alone are a poor criterion of

Where

TABLE

Results

cure

I-PRESENTING CHARACTERISTICS PATIENTS RADIOTHERAPY OR CHEMOTHERAPY IN

(A)

RECEIVING

(B)

success or failure of a treatment regimen. The " quality of life " achieved is difficult to assess, but may be judged to some extent by (1) the success or failure of the palliation of symptoms, (2) the incidence of troublesome sideeffects, (3) the overall limitations imposed by the disease on the patient’s level of activity. On admission to the trial the extent of the primary tumour and metastasis was recorded, together with presence and degree of dyspnoea, cough, pain, and heemoptysis, each graded as none, mild, moderate, or severeaccording to defined criteria. An assessment was also made of the side-effects of treatment, judged by gastrointestinal and haematological complications. The capacity of the patient to lead a normal life was graded as "no " housebound ", or " bedout of house ", restriction ", At 2-monthly intervals thereafter the progress bound ". of measurable disease and the appearance of new disease were recorded together with any change in the patient’s "

Of the 425 patients entered into the Oxford carciof bronchus trial in the period December, 1970, to August, 1973, 68 (16%) had an initial diagnosis of small-cell carcinoma of the bronchus and are the subject of this report.. 37 patients were randomised to receive radiotherapy, and 31 to receive chemotherapy. There were only minor differences in the presenting characteristics of patients in the two groups (table I). All patients have been followed up to Aug. 1, 1974, when there were 2 survivors-1 among those treated with radiotherapy (16 months) and 1 in the chemotherapy group (23 months). noma

Survival Actuarial survival curves drawn by the method of Peto and Pike 1° for both groups are shown in fig. 1. Patients treated with radiotherapy survived signifilonger than those treated with cantly (p