Phase I study of dose-escalated paclitaxel, ifosfamide, and cisplatin (PIC) combination chemotherapy in advanced solid tumours

Citation
C. Kosmas et al., Phase I study of dose-escalated paclitaxel, ifosfamide, and cisplatin (PIC) combination chemotherapy in advanced solid tumours, BR J CANC, 82(2), 2000, pp. 300-307
Citations number
27
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
BRITISH JOURNAL OF CANCER
ISSN journal
00070920 → ACNP
Volume
82
Issue
2
Year of publication
2000
Pages
300 - 307
Database
ISI
SICI code
0007-0920(200001)82:2<300:PISODP>2.0.ZU;2-M
Abstract
Based on the already known in vitro synergy between paclitaxel (taxol), cis platin and oxazophosphorine cytostatics and the broad spectrum of activity of the above drugs we sought to evaluate the paclitaxel (taxol)-ifosfamide- cisplatin (PIC) combination in the outpatient setting in individuals with a variety of advanced solid tumours. Cohorts of patients were entered into s ix successive dose levels (DLs) with drug doses ranging as follows: paclita xel 135-215 mg m(-2) day 1 - (1 h infusion), ifosfamide 4.5-6.0 g m(-2) (to tal dose) - divided over days 1 and 2, and cisplatin 80-100 mg m(-2) (total ) - divided over days 1 and 2. Granulocyte colony-stimulating factor was gi ven from day 5 to 14. Forty-two patients were entered. Eighteen patients ha d 2-8 cycles of prior chemotherapy with no taxanes or ifosfamide(cisplatin was allowed). The regimen was tolerated with outpatient administration in 3 6/42 patients. Toxicities included: grade 4 neutropenia for less than or eq ual to 5 days in 27% of cycles; 5 episodes of febrile neutropenia in three patients at DL-III, -V and -VI. Grade 3/4 thrombocytopenia and cumulative g rade 3 anaemia were seen in 7% and 13% of cycles respectively. Three cases of severe grade 3 neuromotor/sensory neuropathy were recorded at DL-II, -II I, and -V, all after cycle 3. The maximum tolerated dose was not formally r eached at DL-V, but because of progressive anaemia and asthenia/fatigue, it was decided to test a new DL-VI with doses of paclitaxel 200 mg m(-2), ifo sfamide 5.0 g m(-2) and cisplatin 100 mg m(-2) this appeared to be tolerabl e and is recommended for further phase II testing. The response rate was 47 .5% (complete response + partial response: 20/42), The PIC regimen appears to be feasible and safe in the outpatient setting. Care should he paid to n eurotoxicity. Phase II studies are starting in non-small-cell lung cancer, ovarian cancer and head and neck cancer at DL-VI. (C) 2000 Cancer Research Campaign.