93

THERAPY

CHEMOTHERAPY/MISCELLANEOUS

352

CLINICAL STUDY ON OK-432 WITH OR WITHOUT G-CSF IW CDDP AND CQ CHEMOTHERAPY (CX) FOR ADVANCED LUNG CANCER. S. Takamori, T. Kakegawa, "S. Ohtsuka, *H. Hiraki, *H. Ono, and *I. Nakarai, 1st Department of Surgery, Kurume University School of Medicine, Kurume, and *Department of Respiratory Disease, Second Tokyo National Hospital, Japan. The aim of this study was to evaluate whether a

combination of biological response modifiers, such as OK- 432 (picibanil) and G-CSf (lenograstim), is effective in reducing chemotherapy-induced hematologic toxicity (Cx) in patients with advanced lung cancer. CDDP (cisplatin; 70mgfm2, on day 1) and CQ (carboquone; 12mg/m2, on day 2) were administered every 4 or 5 weeks. One KE (Klinische Einheit) of OK-432 was injected i.m. every day from 1 week before the 1st course of Cx to 4 weeks after the 2nd course of Cx (Group I). Group II consisted of group I plus G-CSF (2pg/ky) which was injected S.C. on days 7-14 of each course of chemotherapy. Groups 1+11's neutrophil, leukocyte and platelete counts were compared. A amount of 11-6 and CRP was measured once a week, and correlation coefficients were calculated among 11-6, CRP. and platelets. The subjects were 10 cases in Group I and 11 in Group II. Remarkable side effects related to OK-432 and G- CSF administration were not found. There was no statistical difference on nadir of neutrophil, leukocyte and platelet counts between Group I and Group II. There was a significant correlation between 11-6 and CRP but not between IL-6 and platelets. In conclusion, we could not find a synergistic or additive effect between OK-432 and G- CSF on reducing hematologic toxicity induced by this chemotherapy regimen.

353

PHASE I AND PHAtWACOKtNETlC STUDY OF PACLtTAXEL BY A &HOUR tNl’FlAVBNWS tNFUStON. T. Tamura,Y.Sa&i,Y. Nishiwaidand N.Saijo. National Cancer Center Hospital,Tokyo and National Cancer Center Hospital East, Chiba, Japan

Paclitaxel, a novelantitubularagent, has been administered b a 24-hour infusion inmosttrials. However, recent European-Cans $ Ian bi-factorial designed trial repolted that 3-hr infuekn could produce a similar frequency of hypersensitiiity react&s (HSRs) and a lower frequencyofmye~~,es~granu)ocytope~a. I?the present study paMaxe was administered by a 3-h$$g100: pat&ntswkhsolidtumortodeteninethemaximum (MID) and to descdba the pharmacokinstics of pa&axe1 on this schedule in comparison with those in our previous phase I study using a 24hour mnfusion. Twenty-four pat!ents reoeived one of six levels of paditaxel, 105,135,180,210,240 and 27Orr@rr$ with premeditations. G-CSF was not used in this study. Granukcytopenia was si hour infusion. Severe H 8

nificantly less severe compared with 24- Rs were not observed, but two patients at

24Omg/& & 27Ort@& had fallen in hypotension state just after finishing pacliiaxel infusion. The grade 3 elsvation of transaminase was observed in one at 24Omg/r$. Dose escalation was stopped at 27Orng/d because of neurotoxicity and granulocytopenia.

EL area under the curve (AUC), and decreases in clearance (CL distribution (Vss) with increasing dose, su pharmacokinetics of

s”’ itaxel

AUC were significan given by a !%%?%%%e?rnax and

y higher compared with 24-hour infusion at the same dose of packil. We ccndude that 27Oms/m2 d pacliiel is intolerable. Additional patients are being entered to a level at 240 n-Q@.