Intrapleural pirarubicin (4'-O-tetrahydropyranyladriamycin) for treatment of malignant pleural effusion.
Pirarubicin (4'-O-tetrahydropyranyladriamycin), a new anthracyline derivative, was administered as a single agent into the pleural cavity of 42 patients (total 46 courses) with malignant pleural effusion at a dose of 20, 40, 60 or 80 mg/body. All 46 courses were evaluable for non-hematological toxicities. Fever and chest pain (> or = WHO grade 2) were seen in 67.4% and 13.0% of courses, respectively. Patients receiving a dose of 80 mg/body developed fever of > or = 39 degrees C in 45.5%, and chest pain lasting more than three days and requiring pentazocine more than three times in 36.4%. In contrast, patients receiving a dose of < or = 60 mg/body presented these toxicities in only 8.6% and 2.9%, respectively. Nausea-vomiting (> or = WHO grade 2) was observed in only 4.3% of the total 46 courses and alopecia was not observed. Thirty-eight courses (36 patients) were evaluable for hematological toxicities. Myelosuppression (leukocyte nadir count < or = 1900, WHO grade 3 or 4) was seen in four courses (10.5%), and thrombocytopenia (< or = 49,000, WHO grade 3 or 4) in only two (5.3%). Although the mean AUC (0-24) for pirarubicin in plasma during the four courses that produced myelosuppression was significantly higher than that during the 11 courses without myelosuppression, the difference in the mean dose was not significant. Furthermore, no significant correlation was shown between dose (mg/m2) and AUC in plasma. It is considered that myelosuppression is not a dose-related toxicity at a dose of 20-80 mg/body. The dose-limiting toxicity was fever or chest pain, although unexpected myelosuppression was also encountered. The maximum tolerated dose was 80 mg/body. With regard to clinical efficacy, the overall response rate was 73.7% in 38 evaluable courses (38 patients). The mean T(1/2) of pirarubicin concentration in pleural effusion and plasma was 22.1 h and 8.8 h, respectively. We recommend a dose of 40 or 60 mg/body pirarubicin for this pleurodesic treatment.
Gotoh
T
T
Second Department of Medicine, Kyoto Prefectural University of Medicine.
Tanaka
Y
Y
Fujita
Y
Y
Hiramori
N
N
Fujii
T
T
Arimoto
T
T
Iwasaki
Y
Y
Fukabori
T
T
Nakamura
T
T
Ono
N
N
Nakagawa
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; C027260:pirarubicin