@article{3081560,
    title = "A phase I-II study of docetaxel-ifosfamide-cisplatin (DIP) combination
chemotherapy regimen in advanced nonsmall cell lung cancer",
    author = "Kosmas, C and Tsavaris, NB and Makatsoris, T and Onyenadum, A and and Vadiaka, M and Stavroyianni, N and Sepsas, E and Dimitropoulos, D and and Rokana, S and Kalofonos, HP",
    journal = "International Journal  of Cancer",
    year = "2002",
    volume = "98",
    number = "1",
    pages = "141-147",
    publisher = "Wiley-Liss, Inc.",
    issn = "0020-7136",
    doi = "10.1002/ijc.10162",
    keywords = "docetaxel; ifosfamide; cisplatin; chemotherapy; nonsmall cell lung
cancer",
    abstract = "In an attempt to develop more effective chemotherapy regimens in
advanced nonsmall cell lung cancer (NSCLC), we evaluated
docetaxel-ifosfamide-cisplatin (DIP) based on our previous experience
with paclitaxel-ifosfamide-cisplatin. Patients with advanced NSCLC
(stages III-IV), WHO-PSless than or equal to2, no prior chemotherapy and
unimpaired hematopoietic and organ function were eligible. Chemotherapy
was administered in successive dose levels (DLs) and included docetaxel
(80100 rng/m(2) day 1), ifosfamide (4-5 g/m(2)) and cisplatin (80100
mg/m(2)), both divided over days I and 2 every 21 days. G-CSF
(lenograstin) was administered from days 4-13. Fifty-five patients were
accrued (phase 1: IS; phase II: 40) and all are evaluable for response
and toxicity: median age = 58 (40-72); PS = 1 (0-2); gender = 48 males,
7 females; stages IIIA = 8, 11113 = 19, IV = 28; and histologies were
adenocarcinoma (29), squamous (20), large cell (6). Metastatic sites at
diagnosis included lymph nodes (33), bone (8), liver (6) brain (6), lung
nodules (9), adrenals (7) and soft tissue (1). The dose-limiting
toxicity (DLT) was reached at DL4 (Docetaxel: 100 mg/m(2)-Ifosfamide: 5
g/m(2)-Cisplatin: 100 mg/m(2)) consisting of 2 cases of febrile
neutropenia (FN), and DL3 (Docetaxel: 100 mg/m(2)-Ifosfamide: S
g/m(2)-Cisplatin: 80 mg/m2) was considered as the maximum tolerated dose
(MTD) and recommended for further phase 11 testing. Among evaluable
patients in phase 11, 31146 (67%; Cl = 54-81%) responded; 4 were
complete responses, 27 partial responses, 12 with stable disease and 3
with progressive disease. The median response duration was 7 months
(2-21 +), median time to progression (TTP) 8 months (1-23 +) and median
overall survival (OS) 13 months (2-23 +). The 1-year survival was 57%.
Grade (Gr) 314 toxicities included neutropenia 39146 with 27 developing
Gr4 ( less than or equal to7 days) and 20% FN managed successfully with
broad-spectrum antibiotics, thrombacytopenia Gr3 3/46-Gr4 1/46, no Gr3
neuropathy, Gr1-2 CNS toxicity in 12, no renal toxicity, IS Gr2
myalgias, 17 Gr2 diarrhea and 10 Gr3 vomiting. In the present phase I-II
study, DIP appears highly active and tolerable in advanced NSCLC in the
outpatient setting. Randomized comparisons to current standard 2-drug
regimens will be warranted. (C) 2002 Wiley-Liss, Inc."
}