Phase I-II study of dose intensified chemotherapy with filgrastim and thymopentin in patients with advanced cancer.
BACKGROUND
Carboplatin (CBDCA), cyclophosphamide (CTX) and etoposide (VP-16) combination chemotherapy is active in many tumors. A phase I-II study was designed in order to verify toxicity, maximum tolerated dose and activity of CBDCA, CTX and VP-16 given with Granulocyte Colony Stimulating Factor (G-CSF) and thymopentin (TP5), without bone marrow support.


METHODS
A group of 12 heavily pretreated patients (PTS), 9 breast cancer, 2 small cell lung cancer and 1 gastric cancer, received fourteen courses of the described combination chemotherapy. Previous treatments were as follows: surgery in 10 PTS, radiotherapy in 7 PTS, chemotherapy in all PTS (median of 9 courses per patient). CBDCA, CTX, VP-16 were given over 3 days. CBDCA doses were calculated and expressed with the area under the concentration versus time curve (AUC). The dose range were as follows: CBDCA AUC 5.5-11 (400-800 mg/m2), CTX 1500-2500 mg/m2, VP-16 450-550 mg/m2, G-CSF was given 5 mg/kg/day from day 4 to day 17. TP5 was given, on alternate days, 1 mg/ kg from day 4 to day 30.


RESULTS
6 PTS developed fever > 38 degrees C for a median (M) duration of 4 days. 4 PTS required platelet support (M of 12 units) and 3 PTS red blood cells support (M of 2 units). Maximum tolerated dose was CBDCA AUC of 8, CTX 2000 mg/m2 and VP16500 mg/m2. No treatment related death occurred. Ten patients had responses and two had disease stabilisation. At the present time 5 PTS are alive and median overall survival is 13 months.


CONCLUSIONS
These data indicate that dose intensified CT with the support of G-CSF and TP5 may be delivered safely and shows activity in heavily pre-treated patients.
Recchia
F
F
Division of Internal Medicine (Oncology Unit), Civil Hospital Avezzano, Rome.
De Filippis
S
S
Ginaldi
L
L
Quaglino
D
D
Gulino
A
A
Frati
L
L
Rea
S
S
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004608:Eligibility Determination; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D010166:Palliative Care; D011994:Recombinant Proteins; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016305:Thymopentin / Q000008:administration & dosage / Q000627:therapeutic use*
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016305:Thymopentin; D000069585:Filgrastim