Abstract
Cisplatin and carboplatin are both active in ovarian cancer with different toxicity profiles; thus, dose intensification may be possible by combining them. The aim of the present study was to determine the maximum tolerated dose of carboplatin combined with fixed doses of cisplatin and cyclophosphamide without and with support of lenograstim. Cisplatin (60 mg/m2), cyclophosphamide (600 mg/m2) and carboplatin (starting dose 200 mg/m2) were given on day 1 every 3 weeks for 4 cycles. Escalated dose levels for carboplatin were planned by increments of 50 mg/m2 per level. Lenograstim (L) (150 μg/m2/day subcutaneously) was given in case of grade 4 leukopenia (levels without support) or from day 5 up to leukocyte >10,000/mm3 after nadir (levels with support). Four levels were studied (200, 250, 250 + lenograstim, 300 + lenograstim) with 7, 7, 8, and 7 patients enrolled, respectively. Unacceptable toxicity was induced in 1 patient at the level 1 (grade 4 thrombocytopenia), in 4 patients at the level 2 (2 prolonged grade 2 leukopenia, 1 grade 4 leukopenia with concomitant grade 4 thrombocytopenia and I grade 4 thrombocytopenia), in 1 patient at the level 2 + L (grade 4 thrombocytopenia) and in 3 patients at the level 3 + L (3 grade 4 thrombocytopenia). Thus, 200 mg/m2 and 250 mg/m2 were defined as carboplatin MTDs without and with lenograstim support, respectively. Median total platinum (cisplatin + 1/4 carboplatin) delivered dose-intensities were 33, 32, 38 and 44 mg/m2/week at the four levels, respectively. Hematological toxicity was overall mild. In no case was febrile neutropenia recorded. Grade 4 thrombocytopenia was always transient and never symptomatic. Grade 3 vomiting was the only severe non-hematological toxicity reported in 5 patients. Out of 16 patients with measurable disease, 11 objective responses were obtained (5 complete and 6 partial) for an overall response rate of 69% (95% exact CL 41-89%). Recommended dose of carboplatin is 200 mg/m2 without and 250 mg/m2 with support of lenograstim when combined with cisplatin 60 mg/m2 and cyclophosphamide 600 mg/m2. Dose limiting toxicity is persistent leukopenia without and grade 4 thrombocytopenia with support of lenograstim.
| Original language | English |
|---|---|
| Pages (from-to) | 175-180 |
| Number of pages | 6 |
| Journal | International Journal of Oncology |
| Volume | 11 |
| Issue number | 1 |
| Publication status | Published - 1997 |
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Keywords
- Carboplatin
- Cisplatin
- Ovarian neoplasms
- Platinum dose-intensity
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Phase I study of carboplatin, cisplatin, and cyclophosphamide without and with lenograstim for the treatment of ovarian cancer. / Pignata, Sandro; Lauria, Rossella; Perrone, Francesco; Ferrari, Ettore; Biondi, Edoardo; Maffeo, Antonio; Morabito, Alessandro; Graziano, Raffaele; Carlomagno, Chiara; De Placido, Giuseppe; Gallo, Giro; Bianco, Angelo Raffaele; Pergola, Mario; De Placido, Sabino.
In: International Journal of Oncology, Vol. 11, No. 1, 1997, p. 175-180.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phase I study of carboplatin, cisplatin, and cyclophosphamide without and with lenograstim for the treatment of ovarian cancer
AU - Pignata, Sandro
AU - Lauria, Rossella
AU - Perrone, Francesco
AU - Ferrari, Ettore
AU - Biondi, Edoardo
AU - Maffeo, Antonio
AU - Morabito, Alessandro
AU - Graziano, Raffaele
AU - Carlomagno, Chiara
AU - De Placido, Giuseppe
AU - Gallo, Giro
AU - Bianco, Angelo Raffaele
AU - Pergola, Mario
AU - De Placido, Sabino
PY - 1997
Y1 - 1997
N2 - Cisplatin and carboplatin are both active in ovarian cancer with different toxicity profiles; thus, dose intensification may be possible by combining them. The aim of the present study was to determine the maximum tolerated dose of carboplatin combined with fixed doses of cisplatin and cyclophosphamide without and with support of lenograstim. Cisplatin (60 mg/m2), cyclophosphamide (600 mg/m2) and carboplatin (starting dose 200 mg/m2) were given on day 1 every 3 weeks for 4 cycles. Escalated dose levels for carboplatin were planned by increments of 50 mg/m2 per level. Lenograstim (L) (150 μg/m2/day subcutaneously) was given in case of grade 4 leukopenia (levels without support) or from day 5 up to leukocyte >10,000/mm3 after nadir (levels with support). Four levels were studied (200, 250, 250 + lenograstim, 300 + lenograstim) with 7, 7, 8, and 7 patients enrolled, respectively. Unacceptable toxicity was induced in 1 patient at the level 1 (grade 4 thrombocytopenia), in 4 patients at the level 2 (2 prolonged grade 2 leukopenia, 1 grade 4 leukopenia with concomitant grade 4 thrombocytopenia and I grade 4 thrombocytopenia), in 1 patient at the level 2 + L (grade 4 thrombocytopenia) and in 3 patients at the level 3 + L (3 grade 4 thrombocytopenia). Thus, 200 mg/m2 and 250 mg/m2 were defined as carboplatin MTDs without and with lenograstim support, respectively. Median total platinum (cisplatin + 1/4 carboplatin) delivered dose-intensities were 33, 32, 38 and 44 mg/m2/week at the four levels, respectively. Hematological toxicity was overall mild. In no case was febrile neutropenia recorded. Grade 4 thrombocytopenia was always transient and never symptomatic. Grade 3 vomiting was the only severe non-hematological toxicity reported in 5 patients. Out of 16 patients with measurable disease, 11 objective responses were obtained (5 complete and 6 partial) for an overall response rate of 69% (95% exact CL 41-89%). Recommended dose of carboplatin is 200 mg/m2 without and 250 mg/m2 with support of lenograstim when combined with cisplatin 60 mg/m2 and cyclophosphamide 600 mg/m2. Dose limiting toxicity is persistent leukopenia without and grade 4 thrombocytopenia with support of lenograstim.
AB - Cisplatin and carboplatin are both active in ovarian cancer with different toxicity profiles; thus, dose intensification may be possible by combining them. The aim of the present study was to determine the maximum tolerated dose of carboplatin combined with fixed doses of cisplatin and cyclophosphamide without and with support of lenograstim. Cisplatin (60 mg/m2), cyclophosphamide (600 mg/m2) and carboplatin (starting dose 200 mg/m2) were given on day 1 every 3 weeks for 4 cycles. Escalated dose levels for carboplatin were planned by increments of 50 mg/m2 per level. Lenograstim (L) (150 μg/m2/day subcutaneously) was given in case of grade 4 leukopenia (levels without support) or from day 5 up to leukocyte >10,000/mm3 after nadir (levels with support). Four levels were studied (200, 250, 250 + lenograstim, 300 + lenograstim) with 7, 7, 8, and 7 patients enrolled, respectively. Unacceptable toxicity was induced in 1 patient at the level 1 (grade 4 thrombocytopenia), in 4 patients at the level 2 (2 prolonged grade 2 leukopenia, 1 grade 4 leukopenia with concomitant grade 4 thrombocytopenia and I grade 4 thrombocytopenia), in 1 patient at the level 2 + L (grade 4 thrombocytopenia) and in 3 patients at the level 3 + L (3 grade 4 thrombocytopenia). Thus, 200 mg/m2 and 250 mg/m2 were defined as carboplatin MTDs without and with lenograstim support, respectively. Median total platinum (cisplatin + 1/4 carboplatin) delivered dose-intensities were 33, 32, 38 and 44 mg/m2/week at the four levels, respectively. Hematological toxicity was overall mild. In no case was febrile neutropenia recorded. Grade 4 thrombocytopenia was always transient and never symptomatic. Grade 3 vomiting was the only severe non-hematological toxicity reported in 5 patients. Out of 16 patients with measurable disease, 11 objective responses were obtained (5 complete and 6 partial) for an overall response rate of 69% (95% exact CL 41-89%). Recommended dose of carboplatin is 200 mg/m2 without and 250 mg/m2 with support of lenograstim when combined with cisplatin 60 mg/m2 and cyclophosphamide 600 mg/m2. Dose limiting toxicity is persistent leukopenia without and grade 4 thrombocytopenia with support of lenograstim.
KW - Carboplatin
KW - Cisplatin
KW - Ovarian neoplasms
KW - Platinum dose-intensity
UR - http://www.scopus.com/inward/record.url?scp=12644263414&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12644263414&partnerID=8YFLogxK
M3 - Article
C2 - 21528198
AN - SCOPUS:12644263414
VL - 11
SP - 175
EP - 180
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 1
ER -