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paclitaxel 1 1 14 2 2 14 3 22 63 T4N3M1 stage Cisplatin CDDP paclitaxel TXL 1 grade 3 carboplatin CBDCA TXL 2 regimen 2 American Society of Clinical Oncology ASCO 1 regimen Key words: paclitaxel carboplatin NSCLC stage 1 I : 63 : : : 2 3 : 12 11 12 15 Table 1 Laboratory findings Hematology WBC Ba Eo Neu Lym Mo Hb Plt Biochemistry TP Alb Na K Cl Ca IP 6,49 µl 8 4 8 74 7 14 8 4 9 15 1 g dl 18 2 1 4 µl 6. g dl 3 1 g dl 137 meq L 4 3 meq L 17 meq L 8 3 mg dl 4 mg dl T Bil BUN Cr GOT GPT LDH ALP KL 6 Serological tests CRP ESR Tumor marker CEA SCC Pro GRP 6 mg dl 16 1 mg dl 1 mg dl 31 U L 21 U L 952 U L 371 U L 5,493 U ml 55 mg dl 7 mm h 62 ng ml 2 4 ng ml 43 4 pg ml 6 2 2

Fig. 1 Chest radiography on first admission showing diffuse ground glass opacities in both lung fields. Fig. 3 Bronchoscopic findings of the left main bronchus on admission showing reddish and edematous mucosa. Fig. 2 Chest CT scans on first admission showing infiltration and reticulonodular shadows in both lung fields. Fig. 4 Transbronchial lung biopsy specimen obtained from lt. B 1 2 3 B 4 5 spur showing moderately differentiated adenocarcinoma 2 21 Jan. Feb. Mar. Apr. May June July Relapse Aug. Sept. Oct. CDDP CBDCA TXL VNR GEM (8 mg/m 2 ) (AUC 5) (18 mg/m 2 ) (2 mg/m 2 ) (1, mg/m 2 ) Toxicities Nausea 3 ANC 3 3 4 4 4 4 Neuropathy 2 2 2 2 Fig. 5 Clinical course.

Fig. 6 Chest radiography showing almost normal status after 3 courses of chemotherapy. Fig. 8 Chest radiography on second admission showing diffuse ground glass opacities and infiltrates in both lung fields. Fig. 7 Chest CT scans showing almost normal status after 3 courses of chemotherapy. Fig. 9 Chest CT scans on second admission showing infiltration and reticulonodular shadows in both lung fields. : 172 cm 65 kg 142 8 torr 84 35.3 Table 1 : LDH KL 6 CEA X Fig. 1 : X CT Fig. 2 : CT Fig. 3 : Fig. 4 Fig. 5 : T4N3M1 Stage 13 1 23 cisplatin CDDP 8 mg m 2 paclitaxel TXL 18 mg m 2 1 2 grade Gr. 3 carboplatin CBDCA TXL regimen 2 3 G CSF 2

3 Fig. 6 CT Fig. 7 1 Fig. 8 CT Fig. 9 regimen 2 regimen vinorelbine VNR gemcitabine GEM regimen 6 II TXL Taxus baccata 1 32.2 1 22 2 CBDCA DNA DNA 55 62 3 4 Eastern Cooperative Oncology Group ECOG 1594 trial 2 American Society of Clinical Oncology ASCO Arm A cisplatin: CDDP TXL Arm B GEM CDDP Arm C docetaxel: DOC CDDP Arm D TXL CBDCA 4 21 22 17 17 Arm D 1 31 36 31 34 Arm D TXL CBDCA 5 7 CDDP TXL regimen CBDCA TXL CDDP TXL 1 CBDCA TXL 2 3 1 regimen regimen VNR GEM CDDP CBDCA 8 Glutathione GSH glutathione S transferase GST 9 glutathione S conjugate export pump GS X pump ATP 1 TXL 11 P glycoprotein Pgpmultidrug resistance associated protein: MRP 12 second line GEM CBDCA DNA VNR TXL first line second line 1 Eric K R, Ross C D, Richard J J, et al.: Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol. Cancer research 48: 493 41, 1988 2 : Paclitaxel 46 5 : 33 43, 1997 3 Laohavinij S, Maoleekoonpairoj S, Cheirsilpa A, et al.: Phase study of paclitaxel and carboplatin for advanced non small cell lung cancer. Lung Cancer 26: 175 185, 1999 4 Langer C J, Leighton J C, Comis R L, et al.: Paclitaxel and carboplatin in combination in the treatment of advanced non small cell lung cancer: Aphase toxicity, response, and survival analysis. J Clin Oncol 13 8 : 186 187 1995 5 Johnson D H, Zhu J, Schiller J H, et al.: E 1594 A randomized phase trial in metastatic non small cell lung cancer NSCLC outcome of PS 2 patients Pts : AnEasternCooperative Group Trial (ECOG). Prog Proc Am Soc Clin Oncol 18: 461 a. abstract, 1999 6 Schiller J H, Harrington D, Sandler A, et al.: A randomized phase trial of four chemotherapy regimens in advanced non small cell lung cancer NSCLC Prog Proc Am Soc Clin Oncol 19: 1 a.

abstract 2 7 Schiller J H, Harrington D, Belani C P, et al.: Comparison of four chemotherapy regimens for advanced non small cell lung cancer. N Engl J Med 346 2 : 92 98 22 8 Misawa T, Kikkawa F, Maeda O, et al.: Establishment and characterization of acquired resistance to platinum anticancer drugs in human ovarian carcinoma cells. Jpn J Cancer Res 86: 88 94, 1995 9 Kenneth D T: Glutathione associated enzymes in anticancer drug resistance. Cancer Research 54: 4313 432, 1994 1 Ishikawa T: The ATP dependent glutathione S conjugate export pump. Trends Biochem Sci 17: 463 468, 1992 11 Giannakakou P G, Sackett D L, Kang Y K, et al.: Paclitaxel resistant human ovarian cancer cells have mutant beta tubulins that exhibit impaired Paclitaxel driven polymerization. J. Biol. Chem. 272: 17118 17125, 1997 12 Loe D W, Deeley R G, Cole S P C: Biology of the multidrug resistance associated protein, MRP. Eur JCancer32A:945 957, 1996 Acaseoflung adenocarcinoma was successfully treated with combination therapy of platinum anticancer drugs and paclitaxel Toru Murakami Shin Kawai Hajime Goto and Hiroyuki Kobayashi First Department of Internal Medicine Kyorin University School of Medicine 6 2 2 Shinkawa Mitaka Tokyo 181 4 Japan A 63 year old man admitted for persistent cough and sputum was found in detailed examinations to have advanced lung adenocarcinoma T4N3M1 stageone course of combination chemotherapy of cisplatin and paclitaxel was administered. Since grade nausea developed they were switched to a combination of carboplatin and TXL which was administered for 2 coureses. All subjective symptoms were resolved and image findings particularly ground glass opacities spreading over the bilateral lung fields completely disappeared. Cancer recurred about 1.5 months later while he was followed up as an outpatient. None of subsequent chemotherapy regimens were effective. This phenomenon suggesting tolerance or cross tolerance of drugs is now being studied and is considered an important issue in chemotherapy for non small cell lung carcinoma.