Phase I study of twelve-day prolonged infusion of high-dose ifosfamide and doxorubicin as first-line chemotherapy in adult patients with advanced soft tissue sarcomas.
OBJECTIVE
To determine whether a prolonged 12-day continuous infusion allows the administration of high-dose ifosfamide (IFO) with an acceptable toxicity profile when combined with full-dose doxorubicin (Adriamycin; ADM) as first-line chemotherapy in patients with advanced soft tissue sarcomas.


METHODS
Escalating doses of continuous infusion IFO (8-15 g/m2) given on days 1 to 12 in combination with ADM 75 mg/m2 given on day 8 and prophylactic granulocyte colony-stimulating factor support were administered every 4 weeks to 35 chemonaïve patients with advanced soft tissue sarcomas.


RESULTS
The maximum tolerated dose was IFO 15 g/m2. Hematological toxicity was the main dose-limiting toxicity and was dose dependent. Furthermore, thrombocytopenia was cumulative. Grade 4 (WHO) neutropenia and thrombocytopenia were recorded in 48% and 14% of courses, respectively. Eight patients experienced febrile neutropenia. A partial response was observed in 16 out of 30 assessable patients [53%, 95% confidence interval (CI) 25-63]; median time to progression was 25 weeks (range 4-91).


CONCLUSIONS
This study proved that a prolonged 12-day continuous infusion allows an increase in the total IFO dose that can be safely combined with ADM. A multicentric phase II study by the Italian Sarcoma Group to assess its antitumor activity is currently ongoing in patients with advanced soft tissue sarcomas.
De Pas
T
T
Division of Medical Oncology, European Institute of Oncology, Milan, Italy. tommaso.de-pas@ieo.it
Curigliano
G
G
Masci
G
G
Catania
C
C
Comandone
A
A
Boni
C
C
Tucci
A
A
Pagani
O
O
Marrocco
E
E
de Braud
F
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
D004317:Doxorubicin; D007069:Ifosfamide