第14回アジア大平洋癌学会(香港，1997)
PHASE I AND II STUDY OF AMRUBICIN (SM5887), A NOVEL 9-AMINO-ANTHRACYCLINE,
FOR ADVANCED NON-SMALL CELL LUNG CANCER
T.Sawa, T.Yoshida, T.Ikoma, M.Toyoda, Y.Ariyoshi*, M.Fukuoka*, K.Furuse*
Division of Respiratory medicine, Gifu Municipal Hospital, Gifu, Japan
* SM5887 Lung Cancer Study Group, Osaka, Japan
Amrubicin (AMR) is a novel, totally synthetic 9-amino-anthracycline. Characteristically,
it is converted to its active form, 13-hydroxy-AMR (13-OH-AMR), which is
10 to 100 times more active than AMR. The experimental data have shown that
AMR resulted in better efficacy by the devided treatment schedule than a
single iv injection due to accumulation of the greater amounts of 13-OH-AMR
in tumor tissues. The present study was conducted to determine the maximum-tolerated
dose (MTD) under the administration of an iv injection of AMR once a day
for 3 consecutive days, and to evaluate its efficacy in previously untreated
patients with non-small cell lung cancer (NSCLC). The phase I study was
started at 40mg/m2 of AMR administered iv daily for 3 days (120mg/m2), and
the dose was raised by 5 mg/m2/day. There were at least 4 patients per dose
level, and a total of 13 patients were treated. The MTD was estimated to
be 50 mg/m2/day (150 mg/m2/course). The dose limiting factors were leukopenia,
neutropenia, thrombocytopenia and gastrointestinal complications. The phase
II study was performed using 45 mg/m2/day for 3 days (135 mg/m2/course)
every 3 weeks. Sixty one patients were enrolled in this study. Of 41 assessable
patients evaluated with extramural review, one CR and 13 PRs were observed
(response rate, 34.1%; 95% CI, 20.1% to 50.6%). The major toxicity (>grade
3) were leukopenia (48.8%) and neutropenia (68.3%). It was concluded that
AMR is an active anthracycline in the treatment of advanced NSCLC.
INTRAPLEURAL ADMINISTRATION OF PIRARUBICIN (THP) FOR THE TREATMENT OF
MALIGNANT PLEURISY USING DOUBLE TUBE THORACOSTOMY DRAINAGE
T. Ikoma.M.D., T. Sawa.M.D., N.Yasuda.M.D., T. Yoshida.M.D., Y. Ohno.M.D.,
M. Toyoda.M.D., H. Fujiwara.M.D.
The Division of Respiratory medicine. Gifu Municipal Hospital. GIFU. 500.
Japan
Malignant pleural effusion are a common accompaniment of advanced lung cancer
that cause significant morbidity for the patients. The efficacy and toxicity
of intrapleural administration of pirarubicin (THP), a derivative of adriamycin,
were evaluated in 25 patients with malignant pleurisy using double tube
thoracostomy drainage. Pirarubicin (40 mg/body) was instilated every week
and 1-4 courses (1.76 courses as mean) were performed until pleural effusion
was controled. The results were as follows.
1) Overall response rate in 22 evaluable cases was 86.3%. Thirteen complete
responses and 6 partial responses were obtained. There were 3 cases of no
change and 3 cases that was non-evaluable. Mean survival time was 7.4 months
and 1 year survival rate was 44.1%. After the treatment, performance status
of the patient was significantly improved (P<0.01).
2) Concerning toxicity, transient fever was seen in 88% (grade 1; 6 cases,
grade 2; 16 cases ), chest pain (25%), anorexia (44%) and nausea (32%).
Each side effects were reversible and tolerable to complete the regimen.
In conclusion, intrapleural administration of pirarubicin with double tube
thoracostomy drainage method was considered to be useful for the treatment
of malignant pleurisy.
