Analysis of the impact of growth factor on the haematological safety of dose-dense regimen in the randomized phase II adjuvant trial BO3

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 605-605
Author(s):  
C. Delbaldo ◽  
D. Serin ◽  
F. Priou ◽  
P. Laplaige ◽  
S. Greget ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cox Model ◽  
Haematological Toxicity ◽  
Safety Data ◽  
Dose Intensity ◽  
Breast Adenocarcinoma ◽  
Sequence Versus ◽  
Randomized Phase Ii ◽  
Dose Dense ◽  
The Impact

605 Background: In a randomized phase II study, P. Piedbois et al. explored a dose-dense docetaxel (T) followed by epirubicin/cyclophosphamide (EC) every two weeks versus the reverse sequence, versus standard-dose docetaxel, epiribucin and cyclophosphamide (TEC) every 3 weeks. The main purpose of this second analysis was to further explore the haematological safety of each regimen in patients receiving primary prophylactic pegfilgrastim. Methods: One hundred patients with node-positive invasive breast adenocarcinoma were randomized between (arm A) docetaxel 75 mg/m2, epiribucin 75 mg/m2 and cyclophosphamide 500 mg/m2 (TEC) every 3 weeks for 6 cycles (35 patients) or (arm B) epiribucin 100 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks for 4 cycles, followed by T 100 mg/m2 (EC→T) every 2 weeks for 4 cycles (31 patients) or (arm C) T→ EC (34 patients). Among the 99 patients who received chemotherapy, 79 received pegfilgrastim 6 mg subcutaneous day 1 from the first cycle (27 in arm A, 23 in arm B and 29 in arm C). The safety data of these 79 patients were reported here. Results: Our results showed grade 3/4: neutropenia (arm A 30 %, arm B 39 %, arm C 31 %) and febrile neutropenia (FN) (arm A 11 %, arm B 13 %, arm C 3 %), grade 2–4: anaemia (arm A 26 %, arm B 61 %, arm C 55 %) and thrombocytopenia (arm A 15 %, arm B 9 %, arm C 3 %), respectively. Crude proportion and time to toxicity summaries showed that in dose-dense arms, patients allocated to the EC→ T sequence were more exposed to FN than patients allocated to the T→ EC. In the Cox model taking into account all allocated treatment and age, treatment was a predictor of grade 2–4 anaemia, whereas age was significantly correlated to grade 2–4 thrombocytopenia. There was no clear relationship between haematological toxicity and dose intensity across all treatment arms. Except for nausea (17 % versus 3 %) and neurological toxicity (13 % versus 3 %), non-haematological toxicities were similar in arm B and C. Conclusions: These analyzes confirmed that dose-dense regimens EC→ T or T→ EC are feasible with pegfilgrastim primary prophylaxis. The T→ EC sequence seems to be associated with a better haematological tolerance, and should be the preferred dose-dense regimen providing similar efficacy. The trial was supported by Amgen. No significant financial relationships to disclose.

A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (CPT-11 + oxaliplatin [IRINOX]) and two standard arms (LV5-FU2 + CPT-11 [FOLFIRI], LV5-FU2 + oxaliplatin [FOLFOX]) in first line metastatic colorectal cancer (MCRC) (FNCLCC Accord 08)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3586-3586
Author(s):  
Y. Becouarn ◽  
M. Ychou ◽  
E. Boucher ◽  
A. Adenis ◽  
L. Cany ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Safety Data ◽  
Dose Intensity ◽  
Median Number ◽  
First Line ◽  
Randomized Phase Ii ◽  
Number Of Cycles ◽  
Age Range

3586 Background: LV5-FU2 + CPT-11 or oxaliplatin (OHP) are standard therapies in first line MCRC. This phase II trial evaluates an experimental regimen of CPT-11 + oxaliplatin, without 5FU. Methods: First line MCRC evaluable patients (pts) were randomized to receive, every two weeks, either: Arm A = OHP 85 mg/m2 d1 followed by CPT-11 180 mg/m2 (IRINOX), or Arm B = simplified LV5-FU2 (leucovorin 200 mg/m2 as a 2 h-infusion d1, 5FU bolus 400 mg/m2 d1, and 5FU continuous infusion 2400 mg/m2 d1–2) and CPT-11 180 mg/m2 d1 (FOLFIRI), or simplified LV5-FU2 and OHP 85 mg/m2 d1 (FOLFOX). Results were combined for the two standard arms (FOLFIRI + FOLFOX). Results: 80 pts were included between 09/2002 and 04/2005, 40 in IRINOX (arm A), 20 each in FOLFIRI and FOLFOX (arm B). Pts characteristics (A:B): M/F = 27/13:29/11; median age (range): 63 (41–76):61 (47–75); PS (0/1/2): 16/21/3:16/22/2; median number of cycles (range): 8.0 (1–16):12 (1–26). Safety data: no toxic death. IRINOX (318 cycles): NCI G3–4 neutropenia, 43.6% (pts), 14.7% (cycles); G3–4 neurotoxicity, 17.9% (pts), 5.0% (cycles); G3–4 diarrhea, 33.3% (pts), 5.3% (cycles). FOLFIRI (238 cycles) and FOLFOX (186 cycles): G3–4 neutropenia, 40% (pts) and 23.8% (pts) respectively (8.8% and 7.6% of cycles); G3–4 neurotoxicity, 0% and 14.3% (pts), 0% and 2.7% (cycles); G3–4 diarrhea 15% and 0% (pts), 2.1% and 0% (cycles). Median relative dose-intensity was 0.86 (0.57–1.0) for CPT-11, 0.86 (0.57 -1.0) for OHP in the IRINOX arm. We observed 21 PR in the IRINOX arm, 19 PR and 2 CR in the 2 control arms, for an ORR = 52.5%, 90% CI (38–66). Median follow-up: 17 months, median PFS for IRINOX: 8.4 months. Conclusions: The combination of CPT-11 and OHP (IRINOX) at these doses, every 2 weeks, appears safe and active in first line MCRC. [Table: see text]

scholarly journals MA 17.06 Safety Data from Randomized Phase II Study of CDDP+S-1 vs CDDP+PEM Combined with TRT for Locally Advanced Non-Squamous NSCLC

2017 ◽  
Vol 12 (11) ◽  
pp. S1873-S1874
Author(s):  
A. Ono ◽  
T. Takahashi ◽  
S. Niho ◽  
T. Yoshida ◽  
T. Akimoto ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Safety Data ◽  
Randomized Phase Ii

Capecitabine, an Oral Fluoropyrimidine Carbamate With Substantial Activity in Advanced Colorectal Cancer: Results of a Randomized Phase II Study

2000 ◽  
Vol 18 (6) ◽  
pp. 1337-1345 ◽  
Author(s):  
Eric Van Cutsem ◽  
Michael Findlay ◽  
Bruno Osterwalder ◽  
Walter Kocha ◽  
David Dalley ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Dose Intensity ◽  
Patient Characteristics ◽  
Complete Response ◽  
Phase Iii ◽  
Effective Treatment Option ◽  
Randomized Phase Ii

PURPOSE: To evaluate in patients with advanced colorectal cancer (CRC) three treatment regimens of oral capecitabine in order to select the most appropriate regimen for testing in phase III. PATIENTS AND METHODS: Three capecitabine schedules were evaluated in a randomized phase II design: arm A, 1,331 mg/m2/d bid continuously; arm B, 2,510 mg/m2/d bid intermittently (2 weeks on/1 week off); and arm C, 1,657 mg/m2/d plus oral leucovorin 60 mg/d bid intermittently (2 weeks on/1 week off). RESULTS: One hundred nine patients were randomized; 39 patients were assessable for efficacy in arm A, 34 in arm B, and 35 in arm C. Patient characteristics were balanced in the arms. Confirmed tumor responses (partial response [PR] + complete response [CR]) were reported for eight patients with two CRs (21%; 95% confidence interval [CI], 9% to 36%) in arm A, eight patients with one CR (24%; 95% CI, 11% to 41%) in arm B, and eight patients with two CRs (23%; 95% CI, 10% to 40%) in arm C. Median times to progression (TTP) in arms A, B, and C were 127, 230, and 165 days, respectively. Overall, more toxicity was seen with capecitabine plus leucovorin, particularly diarrhea and hand-foot syndrome. There was no grade 3 or 4 marrow toxicity. CONCLUSION: Capecitabine offers a new, effective treatment option as an oral single agent in advanced CRC. Promising overall response rates were reported for all three regimens. The addition of leucovorin to the intermittent regimen had no marked effect on tumor response or median TTP. The intermittent single-agent capecitabine schedule is proposed for phase III evaluation, based on considerations of toxicity, dose-intensity, response rate, and TTP.

Randomized Phase II Trial of Docetaxel Plus Thalidomide in Androgen-Independent Prostate Cancer

2004 ◽  
Vol 22 (13) ◽  
pp. 2532-2539 ◽  
Author(s):  
William L. Dahut ◽  
James L. Gulley ◽  
Philip M. Arlen ◽  
Yinong Liu ◽  
Katherine M. Fedenko ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Weight ◽  
Phase Ii ◽  
Low Molecular Weight Heparin ◽  
Phase Ii Trial ◽  
Low Molecular Weight ◽  
Randomized Phase Ii ◽  
The Impact ◽  
Docetaxel Group ◽  
Androgen Independent

Purpose Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC. Methods Seventy-five patients with chemotherapy-naïve metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m2 intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression. Results After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P = .32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group. Conclusion In this randomized phase II trial, the addition of thalidomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination.

The Impact of Relative Dose Intensity on Response and Survival in a Series of 180 Newly Diagnosed Patients with Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2671-2671
Author(s):  
Filippo Russo ◽  
Gino Svanera ◽  
Paola Della Cioppa ◽  
Gaetano Corazzelli ◽  
Ferdinando Frigeri ◽  
...  
Keyword(s):  
Survival Rates ◽  
Dose Intensity ◽  
Complete Response ◽  
Relative Dose Intensity ◽  
Rank Statistic ◽  
Cycle Period ◽  
Newly Diagnosed ◽  
Exact Test ◽  
Dose Dense ◽  
The Impact

Abstract To improve ABVD results we first developed a protocol which adds G-CSF to the standard ABVD treatment. From March 1997 to May 2004 69 patients with HL were treated with ABVD+G-CSF and 22 with a standard ABVD. Recently we designed a new dose-dense and dose-intensity ABVD scheme (escABVD-21) for advanced HL; in this new schedule the adriamycin was escalated from 25 to 35 mg/m2 (cycles 1,2,3,4) and the inter-cycle period was shortened from 28 to 21 days (for all 6 cycles); primary G-CSF was administered from d3 to d8 and drugs were delivered at d10 and d21 of every cycle. From June 2004, 19 patients were treated with this protocol. Relative dose-intensity (RDI) was calculated for any of these 110 newly diagnosed HL patients treated with ABVD. The results were also compared with a historical group of 70 patients who had undergone hybrid MOPP/ABVD. HL patients received from 4 to 8 cycles of CT +/− IF-RT. Patients were divided in 4 groups according to the RDI. The first group included 20 (11%) pts with RDI less than 0.80; the 2nd group, 64 (36%) pts with RDI values between 0.80 and 0.95, the 3rd group, 74 (42%) pts with RDI values between 0.96 and 1.10 and, finally, the 4th group included pts with RDI values of more than 1.10. In Tab 2 we report the CR, EFS and OS rates according to the 4 levels of RDI. Figures 1 shows EFS curve according to Kaplan-Meyer. Response and survival rates of groups 1,2,3 and 4 were: 50%vs91%vs97% vs 100%, for CR (p<0.0001); 20%vs78%vs92%vs100% for EFS (p< 0.0001); and 25%vs91%vs99%vs100% for OS (p< 0.0001). The best progression rates of CR, EFS and OS were seen in patients with RDI >1.10. In particular, the new dose-dense and dose-intensity escABVD-21 protocol seems very promising in terms of complete response and toxicity profile: 19/19 pts (100%) obtained an early CR; (PET negative at the end of the 2nd cycle), and, as on 8th August 2005, all these19 patients were disease-free. The dose-escalation of adriamycin and the dose-density of the schedule were well-tolerated; toxicity was mild. These results show that subptimal RDI may compromise outcomes proportionally to the level of RDI reduction. On the contrary, Primary G-CSF permits to deliver dose-dense and dose intense schedules such as escABVD-21 maintaining the same profile of toxicity of standard ABVD, higher RDI levels, and consequently, a significant impact on complete response and survival rates. tab1 Presentation features n. of pts male sex age>45 yrs advanced stage E sites>1 bulky B symptoms IPI score ≥ 3 180 92 43 148 23 80 83 56 % 51% 24% 82% 13% 44% 46% 31% tab.2 Response and Survival according to 4 RDI levels RDI level (range 0.5–1.5) N. of pts. (%) CR rate Fisher’s Exact test (2-sided) EFS rate log-rank statistic 0S rate log-rank statistic overall 180(100%) 90% 80% 88% <0.80 20 (11%) 50% 20% 25% 0.80–0.95 64 (36%) 91% 28.391 78% 74.99 91% 96.76 0.96–1.10 76 (42%) 97% 92% 99% >1.10 20 (11%) 100% 100% 100% significance <0.0001 <0.0001 <0.0001 Figure Figure

Capecitabine plus oxaliplatin (XELOX) followed by capecitabine plus irinotecan (XELIRI) in a sequential schedule in first-line metastatic colorectal cancer (MCRC): a phase II multicenter study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13516-13516
Author(s):  
J. Cassinello ◽  
J. V. Álvarez ◽  
M. J. García-López ◽  
E. Pujol ◽  
A. Colmenarejo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Dose Intensity ◽  
Hepatic Function ◽  
Phase Ii Trials ◽  
First Line ◽  
Highly Active ◽  
Sequential Schedule ◽  
Ecog Ps ◽  
The Impact

13516 Background: In phase II trials, XELOX and XELIRI were highly active and well tolerated in first-line MCRC. The aim of this study is to explore the efficacy and safety of XELOX followed by XELIRI as first-line treatment in MCRC. Specifically, we wanted to evaluate the impact of sequential scheduling on the dose-limiting neurotoxicity associated with oxaliplatin accumulation. Methods: Eligible patients (pts) had histologically or cytologically confirmed MCRC, ECOG PS ≤ 2 and adequate bone marrow, renal and hepatic function. Prior chemotherapy for MCRC was not allowed. Pts received 4 cycles of XELOX (capecitabine 1000mg/m2 orally bid d1–14 + oxaliplatin 130mg/m2 i.v. d1, q3w) followed by 4 cycles of XELIRI (capecitabine 1000mg/m2 bid d1–14 + irinotecan 240mg/m2 i.v. d1, q3w). This sequential schedule was repeated until unacceptable toxicity or disease progression. Results: Of the 35 pts analized to date: M/F (69%/31%); median age 68 years (range 41–78); ECOG PS 0–1 (94%); surgery (77%) and adjuvant chemotherapy (31%). 240 cycles (median 6, range 1–16) have been administered. 35 pts received XELOX (123 cycles, median 4), and 21 pts received XELIRI (83 cycles, median 4) in the first sequential schedule. In the second sequential schedule 6 pts received XELOX (22 cycles, median 4) and 4 pts received XELIRI (12 cycles, median 3.5). Median relative dose intensity was 88% for XEL, 96% for OX and 92% for IRI. In 27 efficacy evaluable pts, the ORR was 48% (95% CI, 29–67%). Eight pts were not evaluable due to adverse events (n=6), ongoing treatment (n=1) and lost of follow up (n=1). Conclusions: This sequential schedule is active and well tolerated in first-line MCRC. The improvement/recovery of the oxaliplatin-related neurotoxicity during the XELIRI phase is also promising and allows the re-treatment with oxapliplatin in the next sequence without accumulating neurotoxicity. Final results will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.

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