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INDUCTION OF INTERLEUKIN-6 BY STREPTOCOCCAL PREPARATION OK-432 IN THE TREATMENT OF CARBOPLATIN + ETOPOSIDE FOR ADVANCED LUNG CANCER : A
M.Shinjo, T.Nakano, T.Nakae, T.Nishigaki, T.Nishian, N.lwahashi, T.Hada, K.Higashino. 3rd Dept. of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Carboplatin (CBDCA) is much less toxic than cisplatin, but it is more myelosuppressive with thrombocytopenia being its dose-limiting toxicity. Interleukin-6 (11-s) is known to increase megakatyocytes. Biological response modifier OK432 has been shown to induce various cytokines in vivo. To evaluate the induction of IL-6 by OK432 in
CBDCA-containing treatment, 7 patients with advanced lung cancer (3
SCLC, 4 NSCLC) were treated with CBDCA 300mglm’ i.v on day 1 and VP-16 100mg/mz on days 1 - 3, with OK432 (IKE/day, km) from
day 3 until recovery of leukopenia. When grade 3 or 4 leukopenia was noted, G-CSF was added daily as a single subcutaneous injection
2 pg/kg/day until recovery. IL-6 and TNF-a levels were measured every 2 hours after the injection of OK432 with or without G-CSF,
which were also measured after the injection of OK432 alone. IL-8
values in serum were elevated in 6/7 patients (85.7%) 4 - 6 hours
after the injection of OK432, while they did not increase after the G-CSF injection alone, when compared with basal levels. This
preliminary results suggest that OK432 increase serum IL-8 value in
advanced lung cancer treated with CBDCA + VP-16, thus this hematopoietic support technique may result in prevention of
CBDCA-induced severe thrombocytopenia.
LONG TERM SURVIVAL IN SMALL CELL LUNG CANCER - PROGNOSTIC FACTORS . E. Senkus, J.Jass.em, B. Karnicka-Mlodkowska, A. Badzio, E. Radzikowska, A. Broniek, K. Krawczyk, K. Malak, E. Kowal, R. MoS- Antkowiak, A. Pilarska-Machowicz, A. Prokop, L. Szymaczek-Meyer for the Polish Lung Cancer Cooperative Group.
Prognostic factors for long term survival were analyzed in a group of 719 patients with small cell lung cancer treated within 4 consecutive prospective multicenter trials between 1981 and 1990. 74 patients (10.3%) survived more than 2 years; 30 of them (4.2%) with no evidence of dis- ease. The most significant prognostic determinator was extent of disease: Z-year survival was 13.9% (59/424) in patients with limited disease (LD) vs 5.1% (15/295) in those with extensive disease (ED) (PC.001). Of 138 female patients 24 (17.4%) survived 2 years or more, compared to 8.6% (50/581) of males (pt.01). Initial performance status, weight loss and chemotherapy regimen (for subpopulations of LD and ED) were also found to be significant prognostic factors (~~0.05). Of the group of a-year survivors 51 patients subsequently died (median survival duration 31 months), 10 are alive with cancer or are lost to follow up and 13 are in complete remission with median follow up of 64 months. 20 patients (3.8%) survived more than 5 years. This study confirms the possibility of cure in SCLC, especially in patients with favorable prognostic factors.
TREATMENT-RELATED DEATHS IN SMALL CELL LUNG CANCER (SCLC) TRIALS: CAN PATIENTS AT RISK BE IDENTIFIED? RJ Stephens, DJ Girlin and D Machin for the Briiish Medical Research Council (MR
8 8 ) Lun Cancer Workin
Party (LCWP). MRC Cancer Trials office, 5 haftesbury Roa 8 , Cambridge, UK.
Despite the fact that SCLC is sensitive to chemotherapy, overall survival is poor, with less than 3% of all patients alive at 5 years. In patients with a better prognosis aggressive treatment ma pal ration of symptoms is the main objective, treatment should r
be worthwhile, but for the majority of patient8 for whom
not cause more problems than it resolves, and any risk of major toxicity, especially treatment-related deaths, must be avoided.
The series of 6 multicentre randomised trials in SCLC using a variety of re
LCWP ha8 enable over 2000 patients
problem of treatment-related deaths in detail. An increased risk was observed in the second week after
commencement of the first cycle of chemotherapy, suggesting that of the 10% of patients who died in the first 3 weeks, half were treatment-related. Much less additional risk was observed followina subseauent cvcles. and no increased risk was observe> for patients initkilly receiving surgery or radiotherapy.
Previous oublished work (Radford et al, Eur J Cancer, 1993, 29A, 81-6) suggested an‘ increased risk of sepsis in patients with a Karnofsky score 250, age >50 years and receiving 3 or more chemotherapy drugs. Starting with this model as a basis, we found that our data suggested a refined version incorporating a WHO performance status 22, the use of 4 drugs, and a blood white cell count of >lO,OOO/mm3. In patients with all these risk factors the risk of a treatment-related death rose to 15%.
It is su have identrfre ‘. 2
gested that for patients in the high risk group we , a policy of givin
doses should be tested in a ran 3. the first cycle of drugs at half-
omrsed cltnical trial.
QUALITY OF LIFE (QL) IN RANDOMISED CLINICAL TRIALS: ARE THE DOCTORS ASSESSMENTS AS VALID AS THE PATIENTS? RJ Stephens, for the British Medical Research Council (MRC) Lung Cancer Working Pa
T (Lcwp), MRC Cancer Trials Cffice, 5 Shaftesbury Road, Cam ridge,, UK. The assessment of QL endpoints is becoming
increasingly important in cancer trials, and it is accepted that patient self-report questionnaires are t Yl
enerally e most
accurate method of a8sessrn 8.
QL (especially psychological symptoms). However, in the pa liatrve setting, where QL is most relevant, non-completion of forms due to patients’ deteriorating health can make accurate comparison between treatments diicult. Therefore, if doctors’ and patients’ assessments, particularly of
P hysrcal symptoms, can be shown to be related, It
may be equal y valid to use doctors’ assessments to compare treatments, and thereby more data may be generated.
In two large MRC LCWP trials of palliative treatment, one of over 300 patients in SCLC, the other of over 500 patients in NSCLC, patients completed a Rotterdam Symptom Checklist at each assessment and the doctor recorded information on a few key physical symptoms, using the same 4-point scale. Up to 6 months from randomisation, the overall compliance was 60% for patients and 66% for doctors.
Results from over 2000 comparisons of the doctors’ and patients’ assessments of these symptoms showed high levels of agreement: complete agreement ranging from 63% for cough to 90% for haemo from 94% in R tysis, and agreement wtthin one grade ranging
c est pain to 99% in haemoptysis. There was increasing disagreement with increasing severity, and also a consistent bias towards doctors underestimatin the level of severity of the patients’ symptoms compared wit the patients ,a themselves. Nevertheless, when comparing treatments longitudinally the 2 methods gave similar results, for example in one trial both demonstrated a significant difference in the levels of dysphagia experienced by the 2 treatment groups.