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.

Docetaxel (T) followed by capecitabine (X) as first-line chemotherapy in patients (pts) with metastatic breast cancer (MBC): Preliminary findings from a phase II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10692-10692
Author(s):  
J. L. Bayo ◽  
M. Lomas ◽  
J. Salvador ◽  
M. Ruiz ◽  
A. Moreno
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
First Line ◽  
Recent Trial ◽  
Highly Active ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Ecog Ps

10692 Background: X and T are highly active single agents in MBC. The XT combination leads to superior overall survival (OS), time to progression (TTP) and response rate (RR) vs. T alone in anthracycline-pretreated MBC [O’Shaughnessy et al. J Clin Oncol 2002]. The aim of this trial was to evaluate the efficacy and safety of sequentially administered T then X as first-line treatment in MBC. Methods: Pts ≥ 18 years with previously untreated, HER2neu-negative MBC, ECOG PS ≤ 2, were included in this prospective, multicenter, non-randomized, phase II study. Pts received 3 cycles of T (100mg/m2 d1) followed by 3 cycles of X (1250mg/m2 bid d1–14), every 3 weeks. Results: To date, 38 pts are evaluable for safety and 33 pts for efficacy. Baseline characteristics: median age 54.4 years (range 33–76); PS ≥ 1 50%; 36 (95%) pts had previous (neo)adjuvant anthracyclines, 8 (21%) concomitant with paclitaxel. The most frequent metastatic sites were: bone 47%, nodes 39% and liver 36%. 69% of pts had ≥ 2 metastatic sites. To date, 38 pts have received 3 cycles of T and 33 have also received 3 cycles of X. A total of 195 cycles have been administered: T 108 cycles (median 3, range 1–3); X 87 cycles (median 3, range 1–3). Dose reductions and interruptions for T vs. X were 32 vs. 21% and 21 vs. 21%, respectively. Median relative dose intensity: T 0.97 (range 0.62–1.00), X 0.93 (range 0.26–1.00). T grade 3/4 toxicities (37 evaluable pts): asthenia 19%, mucositis 16%, nausea 13%, febrile neutropenia 11%, rash 5%, diarrhea 5%, infection 3%. X grade 3/4 toxicities (33 evaluable pts): hand-foot syndrome 9%, diarrhea 9%, vomiting 9%, asthenia 6%, nausea 3%, anorexia 3%. In the 33 pts evaluable for efficacy, the RR was 61%, including 4 CRs and 16 PRs. At a median follow-up of 6.1 months, median TTP has not yet been reached. Conclusions: These preliminary results show that the sequential regimen of T followed by X is feasible, effective and well tolerated in first-line MBC, although giving X before T should also be investigated. Findings from a recent trial of XT vs. T followed by X [Beslija et al. ECCO 2005] suggest that XT should be standard in fit poor-prognosis pts with aggressive disease. No significant financial relationships to disclose.

Final results of phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in metastatic colorectal cancer (mCRC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 574-574 ◽  
Author(s):  
Kentaro Yamazaki ◽  
Tomohiro Nishina ◽  
Takeshi Kato ◽  
Takayuki Yoshino ◽  
Yoshinori Miyata ◽  
...  
Keyword(s):  
Survival Rate ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Present Report ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Target Lesion ◽  
Ecog Ps ◽  
The Impact

574 Background: The SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) demonstrated a promising activity with tolerated toxicities compared to mFOLFOX6 in a randomized phase II study for mCRC. We previously reported the promising results of a phase II study of SOL+BV in Gastrointestinal Cancers Symposium 2012 (Kato T, et al.) focusing on early clinical outcomes, overall response rate (ORR), progression free survival (PFS) and safety. The final follow-up (cut-off date Dec 2012) has been completed, and we report up-dated overall survival (OS) and the impact of early objective tumor response (EOTR) on OS in the present report. Methods: The main inclusion criteria were; (1) metastatic colorectal adenocarcinoma, (2) age ≥20 years, (3) no prior chemotherapy, (4) target lesion (RECIST v1.0), (5) ECOG PS 0-1, 6) written informed consent. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week. Oxaliplatin (85 mg/m2) and BV (5 mg/kg) were administered on day 1. This treatment was repeated every 2 weeks. The primary endpoint was ORR confirmed by the independent review committee according to RECIST v1.0. This trial was supported by Taiho Pharmaceutical CO, LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881). Results: From Oct 2009 to Apr 2010, 31 pts were enrolled. Of the eligible 29 pts, median age was 62; PS 0/1 was 24/5; number of metastatic organs 1/≥2 was 15/14. ORR was 86% (95%CI, 68-96), and the median PFS was 15 months (95%CI, 10-26). OS has not reached median with a median follow-up time of 34 months. Two-year survival rate was 72%. EOTR (RECIST sum ≥30% shrinkage) at 6-weeks was observed in 35% of pts. Two-year survival rate in these pts with an EOTR at 6-weeks was 80%, while in other pts without an EOTR at 6-weeks was 68%. The curative resection rate of metastatic lesions was 28%. The incidence (≥10%) of grade 3/4 adverse drug reactions were; neutropenia 20%, hypertension 23%, anorexia 20%, fatigue 17%, diarrhea 10%, and sensory neuropathy 53%. Conclusions: The SOL+BV regimen showed the promising activity for mCRC. The high proportion of EOTR might lead to long survival. Further evaluation of this regimen would be warranted. Clinical trial information: 090881.

Capecitabine (X) compared to X + erlotinib (E) as first-line treatment in patients (pts) with metastatic colorectal cancer (MCRC): Interim efficacy results from a randomized phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14560-14560 ◽  
Author(s):  
M. Vincent ◽  
I. Kerr ◽  
B. Dingle ◽  
M. J. MacKenzie ◽  
M. Sanatani
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
First Line ◽  
Open Label ◽  
Dry Eyes ◽  
Open Label Phase ◽  
Grade 3 ◽  
Ecog Ps

14560 Background: The oral fluoropyrimidine X (Xeloda®) has efficacy, safety and convenience benefits vs. 5-FU/LV in adjuvant / first-line CRC. E (Tarceva®) inhibits epidermal growth factor receptor (EGFR), which predicts poor prognosis. A randomized open-label phase II study was performed to establish activity of X alone vs. X + E (XE) in first-line. Methods: Pts (ECOG PS 0–2 and/or elevated LDH) with MCRC not eligible for immediate surgical metastatectomy and unwilling/unable to undergo combination chemotherapy were randomized to X (1000mg/m2/d bid d1–14 q3w) or XE (X 1000mg/m2/d bid d1–14 q3w + E 150mg/d). A third arm (E alone) was included but dropped after 13 pts, following safety committee review of progressions at first CT scan. Primary endpoint: time to progression (TTP). Results: 59 pts (median age 65y, range 46–84; 44 M, 15 F) have been accrued (X=21; XE=25; E=13). Mean time on study: 3.8 months (range 0.2–12). 9 pts are on active treatment, 21 pts on follow-up and 29 pts have died. Interim efficacy results are available for 50 pts (X n=15; XE n=22, E n=13). There were no significant differences in response rate, median TTP (4.9 vs. 9.2 months) and median overall survival (18.2 vs. 15.1 months) for X vs. XE. Grade 3 adverse events (AEs) with X were diarrhea, nausea, hand-foot syndrome (HFS), angina, dyspnea (all 5%). Corresponding rates of grade 3 AEs with XE were diarrhea (20%), fatigue (16%), stomatitis (12%), HFS (8%), vomiting (8%), dehydration (8%), thrombosis, weight loss, decreased appetite, dry eyes, headache, anxiety, abdominal pain, anorexia, hyponatremia (all 4%). The only grade 4 AEs were skin rash (4%) and subjective weakness (4%) - both XE. Conclusions: Interim results indicate that XE is at least as effective as X alone in first-line MCRC. Recruitment is continuing and further follow-up may help fully determine the potential benefits of adding E to X. [Table: see text] No significant financial relationships to disclose.

A multicentric prospective study of intensive induction chemotherapy (API-AI) in localized osteosarcoma patients: Results of a phase II trial coordinated by the French Sarcoma Group (FSG) and the FNCLCC BECT

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9521-9521 ◽  
Author(s):  
S. Piperno-Neumann ◽  
B. Bui ◽  
J. Blay ◽  
H. Roché ◽  
F. Pichon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Dose Intensity ◽  
Poor Responders ◽  
High Dose ◽  
Severe Toxicity ◽  
Salvage Regimen ◽  
The Impact

9521 Background: Based on the severe toxicity of high dose methotrexate (MTX) in adult patients, an alternative intensive chemotherapy (CT) was designed, associating doxorubicin, cisplatinum and ifosfamide in API-AI regimen. Promising results in 32 patients in a single institution study (Le Cesne ASCO 2004) led to a national multicenter phase II trial coordinated by the FSG of FNCLCC. Methods: Patients with a localized operable osteosarcoma were eligible. API-AI regimen consisted in 2 cycles every 28 days of doxorubicin 60 mg/m2 d1 and d15, cisplatinum 100 mg/m2 d1 and ifosfamide 5g/m2 d2 and d15, with equivalent dose of mesna and lenograstim after each course for 7 days. Good responders ≥95% necrosis (GR) received 2 postoperative API courses, and poor responders <95% necrosis (PR) a salvage regimen of 3 cycles of etoposide 100 mg/m2 d1 to d3 and ifosfamide 4 g/m2 d1 to d3. Results: From March 2001 to January 2004, 43 patients (male/female 28/15) with a median age of 23 years (range 17–50), were included. The median tumor size was 88 mm (13–280). All 43 patients received the preoperative API-AI regimen, with a dose intensity of ≥ 89% of the planned protocol. Toxicity was mainly haematological, with grade 3–4 sepsis, grade 4 neutropenia and thrombocytopenia observed in 12%, 79% and 49% of patients respectively. There was no severe renal and cardiac toxicity. All but 5 patients had a limb sparing surgery performed 77 days (median) after the first cycle (range 56–114 days). Intent to treat analysis showed 16/43 GR (37%). With a median follow-up of 36 months (25–48), the 2 year event-free and overall survival were 74% and 86% respectively. Conclusions: Despite the haematological toxicities, these results compare favorably with other previous induction CT schedules containing MTX in adults. A longer follow-up is required to evaluate the impact of this regimen on overall survival. No significant financial relationships to disclose.

Phase II study of S-1 plus irinotecan (SIR) in patients with advanced colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13508-13508
Author(s):  
A. Goto ◽  
Y. Yamada ◽  
Y. Shimada ◽  
K. Shirao ◽  
T. Hamaguchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Response Rate ◽  
Dose Intensity ◽  
First Line ◽  
Eligibility Criteria ◽  
First Line Therapy ◽  
Highly Active ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Ecog Ps

13508 Background: Infusional fluorouracil and leucovorin (5-FU/LV) plus irinotecan is one of the standard regimens for the treatment of metastatic colorectal cancer (MCRC). S-1, a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and oxonic acid, is an oral DPD inhibitory fluoropyrimidine shown to be very effective as first-line treatment for MCRC. The response rate with S-1 was 35–40% in patients with chemo-naïve MCRC. This study evaluated the efficacy and toxicity of S-1 plus irinotecan (SIR). Methods: Eligible patients had untreated MCRC as confirmed histologically, PS 0–1, adequate organ function, and provided written informed consent. First-line SIR was given in 3-week treatment cycles: intravenous irinotecan 150 mg/m2 (day 1) and oral S-1 40 mg/m2 twice daily for 14 days followed by 7 days of rest. Results: Forty-one patients were enrolled; 40 fulfilled all eligibility criteria, and 1 had double cancers. There were 28 men; median age 60 years (range, 23–74); ECOG PS 0/1, 35/6. The overall response rate was 63% (95%CI, 48–78%). Five patients had a CR, 20 a PR, 11 SD, and 2 PD. Median TTP was 8.0 months (range, 1.4–13.8 months); MST was not reached. The most frequent grade 3/4 toxicities included: neutropenia (17%), diarrhea (15%), and anorexia (12%). One patient had Grade 4 constipation. The relative dose intensity of irinotecan was 84%, and that of S-1 was 79%. Dose reduction of irinotecan was required in 41 of 327 administered cycles, and that of S-1 was required in 15 of 327. Conclusions: SIR is a highly active and convenient first-line therapy for MCRC, with an acceptable toxicity profile. S-1 has the potential to replace infusional 5-FU/LV plus irinotecan for MCRC. 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]

S0204: Melphalan (MEL)-Based Tandem Autotransplants (TAT) for Multiple Myeloma (MM) with Thalidomide/Dexamethasone (TD) Induction and Thalidomide/Prednisone (TP) Maintenance: A Phase II Trial of the Southwest Oncology Group.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3088-3088 ◽  
Author(s):  
Mohamad A. Hussein ◽  
Andrzej J. Jakubowiak ◽  
Vanessa Bolejack ◽  
Jeff Zonder ◽  
John Crowley ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Response Rates ◽  
M Protein ◽  
Phase Ii Trials ◽  
Prognostic Features ◽  
Protein Reduction ◽  
The Impact ◽  
Pbsc Mobilization

Abstract Background: TAT has recently been shown to double the 7-yr event-free (EFS) & overall survival (OS) rates achieved with a single AT (20% & 40%; IFM94). Completion of TAT in most randomized & phase II trials seldom exceeds 70%, due to toxicities encountered with prolonged induction chemotherapy & posed by the 1st AT. TD is effective salvage therapy &, when used up-front, effects high response rates including ~10% CR. Patients and Methods: To reduce induction toxicities & thus deliver TAT in a timely fashion to the majority of pts, SWOG embarked on a trial of TD induction, modest-dose cyclophosphamide (CTX) for PBSC mobilization, melphalan (MEL)-based TAT & subsequent TP maintenance. Results: Between July 2002 and December 2005, 147 newly diagnosed patients with MM were enrolled from 28 institutions. Among 138 eligible, analyzable patients, the median age was 56.5yr (range, 23.2–66.0), 83% were white, 62% male. Baseline prognostic features included serum levels of albumin <3.5g/dL in 21%, beta-2-microglobulin (B2M) >5.5mg/L in 21%, creatinine >=2mg/dL in 7%; ISS stage distribution I-48%, II-30%, III-22%. With a median follow-up of 14mo, 64 patients have come off protocol: 15 patients were removed from study due to adverse events, 10 refused further participation, 14 suffered progression or relapse, 1 died, 9 came off for other reasons, and 15 are presently under review. Therapy was well tolerated except for an increased incidence of hyper-coagulable events at the start of the protocol 27% (8/30); following an amendment to decrease the start dose of thalidomide to 50mg, the incidence of hyper-coagulable events decreased to 7% (7/101). Through the induction and PBSC mobilization phases, 4.4% achieved CR & 64.3% achieved Response (SWOG: >=75% M-protein reduction) or partial response (PR, >=50% M-protein reduction) pre-transplant for an overall response rate of 68.7%. 102 eligible patients proceeded to 1st transplant (74%) and 66 (47%) to 2nd transplant, with a median time to 2nd AT of 8mo and 96% of patients receiving 2nd AT within 4mo from 1st AT. Confirmed and unconfirmed CR after the transplant phase was 22%. Two-year OS from 1st transplant registration among 98 patients was 84% and 2-yr OS from TP maintenance among 62 patients was 87%. Conclusion: Our data show that hyper-coagulable events with the TD regimen could be reduced by decreasing the starting dose of thalidomide from 100mg to 50mg/d. In a multi-institution setting, MEL200-based TAT could be performed safely. Timeliness of the 2nd AT was achieved where 96% of the patients were able to received the procedure within 4 months of the 1st AT. Response rates and quality are promising. Longer follow up should clarify the impact of the improved timeliness of 2nd AT, quality and response rate on PFS and OS.

Phase II study of sequential chemotherapy with cisplatin (P) in combination with infusional 5FU/LV (PFL) followed by irinotecan (Ir) + 5FU/LV (IrFL) followed by docetaxel (T) + 5FU/LV (TFL) in patients (pts) with metastatic gastric carcinoma (MGC) by the Gruppo Oncologio Nord-Ovest (GONO)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15059-15059
Author(s):  
F. Loupakis ◽  
G. Masi ◽  
S. Bursi ◽  
V. Picone ◽  
L. Mentuccia ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Cross Resistance ◽  
First Line ◽  
Sequential Chemotherapy ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Grade 3 ◽  
Ecog Ps

15059 Background: 5FU in combination with P can be considered a standard treatment for MGC. Ir and T are active agents with not complete cross-resistance with P and 5FU. The combination of Ir or T with P and 5FU is feasible but with substantial toxicities. A different way to include Ir and T in the first-line treatment of MGC is to use them sequentially to a P and 5FU containing regimen. Methods: we conducted a phase II study of first-line sequential chemotherapy in MGC pts with measurable disease (RECIST criteria). Treatment consisted of: 3 cycles of PFL (biweekly P 50 mg/sqm d1, LV 200 mg/sqm d1 and 5FU 3200 mg/sqm 48-h c.i. starting on d1) followed by 3 cycles of IrFL (biweekly Ir 180 mg/sqm d1 and 5FU/LV) followed by 3 cycles of TFL (biweekly T 50 mg/sqm d1 and 5FU/LV). Evaluation of disease was performed every 3 cycles. Results: 46 pts have been enrolled. Pts characteristics are: median age = 60 years (37–75), M/F = 36/10, sites of disease (single/multiple) 9/37, ECOG PS 0/1 = 27/19. Treatment was well tolerated. Grade 3–4 non-haematological toxicities were: diarrhea in 2,5% pts with PFL; diarrhea and asthenia in 2,5% and stomatitis in 5% pts with IrFL; stomatitis in 5,7% pts with TFL. Grade 3/4 neutropenia was observed in 14% pts with PFL, 15% with IrFL and 22,9% pts with TFL. Nor febrile neutropenia neither toxic deaths have occurred. Two pts had not evaluable disease and 6 are still receiving treatment. We observed 1 CR and 8 PR with PFL (RR 24%) among the 38 evaluable pts. IrFL improved responses in 10 pts while 4 pts progressed and TFL further improved responses in 6 pts while 5 pts progressed. Response rate at the end of the planned 9 cycles was 40% (4 CR, 11 PR; 95% CI 25–58%). At a median follow-up of 15.5 mos median TTP is 6.8 mos and median OS is 13.5 mos. Conclusions: this sequential treatment is feasible with a very favourable safety profile and produces encouraging results in terms of activity and efficacy in a population of unselected MGC patients. Final data will be presented at the meeting. Partially supported by A.R.C.O. Foundation. No significant financial relationships to disclose.

scholarly journals Evaluation of Treatment Effect with Paired Failure Times in a Single-Arm Phase II Trial in Oncology

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Matthieu Texier ◽  
Federico Rotolo ◽  
Michel Ducreux ◽  
Olivier Bouché ◽  
Jean-Pierre Pignon ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Phase Ii ◽  
Treatment Effect ◽  
Parametric Method ◽  
Design Parameters ◽  
Nonparametric Method ◽  
Operating Characteristics ◽  
Phase Ii Trials ◽  
The Times ◽  
The Impact

In early phase clinical trials of cytotoxic drugs in oncology, the efficacy is typically evaluated based on the tumor shrinkage. However, this criterion is not always appropriate for more recent cytostatic agents, and alternative endpoints have been proposed. The growth modulation index (GMI), defined as the ratio between the times to progression in two successive treatment lines, has been proposed for a single-arm phase II trials. The treatment effect is evaluated by estimating the rate of patients having a GMI superior to a given threshold. To estimate this rate, we investigated a parametric method based on the distribution of the times to progression and a nonparametric one based on a midrank estimator. Through simulations, we studied their operating characteristics and the impact of different design parameters (censoring, dependence, and distribution) on them. In these simulations, the nonparametric estimator slightly underestimated the rate and had slightly overconservative confidence intervals in some cases. Conversely, the parametric estimator overestimated the rate and had anticonservative confidence intervals in some cases. The nonparametric method appeared to be more robust to censoring than the parametric one. In conclusion, we recommend the nonparametric method, but the parametric method can be used as a supplementary tool.

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