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final results of this trial-10 deaths in the first category (1549women) versus only 1 (1562 women) in the second. A simplematernal history of vigorous or reduced fetal activity innormal gravidas at term had already been shown byMathews2s not to be associated with any objective evidence ofdifferences in feto-placental wellbeing. But should not theresults in Neldam’s formal-counting group have made a greatimpact on obstetric practice? The original report seemedalmost too good to be true.26 But the false-negative (the firststillbirth) in Grant’s update24 may help counteract this

feeling, while the Apgar scores in the original paper suggest afalse-positive ("alarm") rate as high as 50%. Neldam27 haslately confirmed, by means of dynamic ultrasound, thatbetween the 28th and 42nd weeks of pregnancy fetal-movement counting reliably reflects fetal activity. Let ushope that someone, somewhere, is repeating the Danishstudy-perhaps just in women with apparently normalpregnancies, and with a sterner method of randomisation.

CHEMOTHERAPY FAILURE IN HODGKIN’S DISEASE

CYCLICAL combination chemotherapy with MOPP

(mustine, vincristine, procarbazine, prednisone) was a majorstep forward in the treatment of advanced Hodgkin’s disease.Previously, with single-agent chemotherapy completeremissions were uncommon and almost all patients were deadby 5 years. In contrast MOPP produces complete remissionin 80% of patients and, of these, two-thirds are disease-free at10 years.’ This impressive achievement still leaves room forprogress, because 50% of patients with advanced Hodgkin’sdisease are not cured by chemotherapy. It seems thatcontinuation of MOPP beyond 6-8 cycles as maintenancetreatment does not improve relapse-free survival. Thereasons for treatment failure in patients not previouslytreated with drugs are not well understood but certain groupsof patients seem less likely than others to achieve a completeremission or more likely to relapse quickly.In a long-term follow-up of the results of MOPP chemo-

therapy de Vita et al. reported that the presence of constitu-tional symptoms was associated with a remission rate of 78%compared with 10007o in the small number who had no suchsymptoms. There was a trend towards a lower remission rateas clinical stage increased, and females remitted rather moreoften than males. Histology and age seemed to have noinfluence on remission rate. The duration of remission in this

study was, however, influenced by histology, those withnodular sclerosing histology having shorter disease-freeintervals (DFI). This was particularly noticeable in thosepatients with nodular sclerosing histology where there was asubtype of lymphocyte depletion in the nodules. Of thepatients without constitutional symptoms, 22 out of 23 didnot relapse, compared with a relapse rate of 37% of those withsymptoms. Patients with clinical stage 4 disease had a shorter

25. Mathews DD. Fetal well-being in gravidas with diminished fetal activity at term. ObstetGynecol 1978; 51: 281-83.

26. Hertogs K, Roberts A, Campbell S. Do fetal movements reflect fetal wellbeing? BrMedJ 1981; 282: 1153-54.

27. Neldam S. Fetal movements: a comparison between maternal assessment and registra-tion by means of dynamic ultrasound. Dan Med Bull 1982, 29: 197-99.

1. Longo DL, Young RC, de Vita VT. Chemotherapy for Hodgkin’s disease: Theremaining challenges. Cancer Treatment Rep 1982; 66: 925-36.

2. Luce JK, Frei E, Gehan EA, et al. Chemotherapy of Hodgkin’s disease-maintenancetherapy vs. no maintenance after remission induction with combination chemo-therapy. Arch Intern Med 1973; 131: 391-95.

3. de Vita VT, Simon RM, Hubbard SM, et al. Curability of advanced Hodgkin’s diseasewith chemotherapy. Ann Intern Med 1980; 92: 587-95.

DFI, as did those with pleural disease, but age had noinfluence on time to relapse. In the Medical ResearchCouncil’s trial of maintenance chemotherapy4 there was asuggestion that early relapse was more frequent in men, inpatients with stage 4 disease, in those with systemicsymptoms, and in those over the age of 40. In the study ofLuce et al. the remission rates were the same for men andwomen, were slightly lower over the age of 60, and wereworse for stage 4B and 4A. Previous chemotherapy loweredthe remission rate (a universal finding), but in previouslyuntreated patients the remission rate was lower if the "bonemarrow reserve" was impaired and full doses could not begiven.A recent small retrospective stUdyS has confirmed these

findings. The complete remission rate was on the low side(61 70). Failure to induce complete remission was related toinadequate drug dose (usually due to drug toxicity) butcomplete remission was less frequent in patients over 40 andin those with constitutional symptoms. Early relapse alsoseemed to be associated with deviations from the planned fulldosage.MOPP chemotherapy therefore seems most likely to fail in

patients with stage 4 disease and with constitutional

symptoms; age over 40, male sex, and nodular sclerosishistology especially of the lymphocyte-depletion subtype, areother probable adverse factors. Additional treatment shouldbe considered in these patients, although their tolerance ofdrug treatment may be lower than that of patients with lessadvanced disease. Bonadonna et al. have reported data,suggesting that the ABVD regimen (doxorubicin, bleomycin,vinblastine, dacarbazine) has a similar remission inductionrate to MOPP and that the cyclic alternation of ABVD withMOPP improves the complete remission and relapse-freesurvival rates in stage 4 disease. Earlier reports of the efficacyof ABVD in MOPP-resistant patients7 have not beenconfirmed by others.8 The discrepancies may be related topatient selection and ABVD may be most effective whengiven to patients undergoing their first treatment. There arealso theoretical reasons9 to support the early use of a "non-cross-resistant" regimen in remission reduction. Theaddition of ABVD to the MOPP regimen seems to give ahigher remission rate in all categories of patients6 and toeliminate the clinical prognostic differences observed withMOPP alone. The 5-year results with MOPP alone were,however, unusually poor and these observations needconfirmation in a larger group of patients with carefulattention to the suspected prognostic factors. The morbidityof chemotherapy is considerable but, in patients at risk ofpoor response or early relapse, the increased toxicity may bejustified.

4. Medical Research Council’s Working Party on Lymphomas. Randomised trial of two-drug and four-drug maintenance chemotherapy in advanced or recurrent Hodgkin’sdisease. Br Med J 1979; i: 1105-08.

5. Armitage JO, Corder MP. Reasons for failure of MOPP to cure Hodgkin’s disease. AmJ Clin Oncol 1982; 5: 315-19.

6. Bonadonna G, Santoro A, Bonfante V, et al. Cyclic delivery of MOPP and ABVDcombinations in stage 4 Hodgkin’s disease: rationale background studies and recentresults. Cancer Treatment Rep 1982; 66: 881-87.

7. Santoro A, Bonadonna G. Prolonged disease-free survival in MOPP-resistant

Hodgkin’s disease after treatment with adriamycin, bleomycin, vinblastine anddacarbazine (ABVD). Cancer Chemother Pharmacol 1979; 2: 101-05.

8. Sutcliffe SB, Wrigley PFM, Stansfeld AG, et al. Adriamycin, bleomycin, vinblastine,and imidazole carboxanmide (ABVD) therapy for advanced Hodgkin’s diseaseresistant to mustine, vinblastine, procarbazine and prednisolone (MVPP). CancerChemother Pharmacol 1979; 2: 209-13.

9. Goldie JH, Coldman AJ. A mathematical model for relating the drug sensitivity oftumours to their spontaneous mutation rate. Cancer Treatment Rep 1979; 63:1727-33.