A phase II trial of irinotecan, 5-fluorouracil and leucovorin in patients with previously untreated advanced colorectal cancer (CRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14599-14599
Author(s):  
N. Lee ◽  
S. Bae ◽  
S. Lee ◽  
D. Kim ◽  
K. Kim ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Control ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Ecog Ps

14599 Background: We prospectively conducted a phase II trial to test the efficacy and safety of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) regimens for the first-line treatment of previously untreated patients with recurrent or metastatic advanced CRC. Methods: Thirty-four previously untreated patients with advanced CRC were enrolled in this study from June 2001 to December 2006. Eligible patients had histologically confirmed adenocarcinoma, no prior systemic therapy in palliative setting, ECOG PS = 2, adequate organ function, written informed consent and at least one measurable disease. The patients received either irinotecan 180 mg/m2 on day 1 with a LV bolus of 200 mg/m2 and a FU bolus of 400 mg/m2, and this was followed by a FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the classic FOLFIRI regimen), or they were treated with a LV bolus of 400 mg/m2 and a FU bolus of 400 mg/m2 followed by a FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. Results: There were 13 females and 21 males with median age of 54 years (range: 41–79). The most common metastatic sites were lung and liver. A total of 262 cycles were administrated with median 6 cycles per patient (range: 1–22). All pts were evaluable for toxicity, and 30 pts for response to the treatment. The objective response rate was 26.4% with 2 complete responses respectively. Sixteen (47%) pts had stable disease and 7 (20.5%) had a progression. The tumor control rate was 73.4%. The median TTP was 5.3 months, and the overall survival was 10.1 months. The prognostic factor for longer TTP and survival was the ECOG performance status (PS). The type of regimens was not affected on response rate, TTP and survival. The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia, diarrhea. The non- hematological toxicities were similar for both treatment groups, with more frequent grade =3 neutropenia being noted for the simplified FOLFIRI regimen. Conclusions: The FOLFIRI regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and tend to show more favorable outcome for patients with good ECOG PS. No significant financial relationships to disclose.

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

Phase II study of irinotecan and paclitaxel for patients with recurrent small cell lung cancer (SCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18011-18011
Author(s):  
T. K. Owonikoko ◽  
S. Ramalingam ◽  
J. Forster ◽  
Y. Shuai ◽  
T. Evans ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Treatment Options ◽  
Objective Response ◽  
Ecog Performance Status ◽  
Stage Design ◽  
Prior Chemotherapy Regimen ◽  
Version 2.0

18011 Background: Recurrent SCLC has a poor prognosis and is devoid of treatment options that improve overall survival. Irinotecan and paclitaxel are both active agents against SCLC, and have synergistic preclinical interactions. We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel for patients with recurrent SCLC. Methods: Patients with SCLC who relapsed following one prior chemotherapy regimen were eligible. Other pertinent inclusion criteria were: ECOG performance status 0–2, adequate bone marrow, hepatic and renal function and willingness to provide informed consent. Patients with untreated brain metastasis were excluded. Paclitaxel (75 mg/m2) and irinotecan (50 mg/m2) were administered on days 1 & 8 of every 3-week cycle. Treatment was continued until progression up to a maximum of 6 cycles or unacceptable toxicity. The primary endpoint was response rate. Toxicity was graded by CTC version 2.0. The simon two-stage design was utilized and the estimated sample size was 55 patients (stage I - 23 patients; stage 2 - 32 patients). The study has a 90% power to detect a response rate of 30%, with an alpha error rate of 10%. Results: 55 patients have been enrolled and complete data are available for 32 patients at the time of this report. Patient baseline characteristics are: male 53%, PS 0–44%; PS 1–47% and PS 2–6%. The median age is 61 years. Fifteen patients received ≥ 4 cycles. Salient grades 3–5 toxicities seen: neutropenia (13%), fatigue (13%); diarrhea (3%), hypersensitivity (3%) and hyponatremia (3%).The objective response rate is 37% (95% CI 19%-55%) with 9 PRs and 1 CR. Additional 8 patients (24%) had stable disease. The median survival is 19.6 weeks (95% CI 15.1–29.4) and the 1-year survival rate is 15%. Conclusions: The combination of irinotecan and paclitaxel is well tolerated and has promising anti-cancer activity in recurrent SCLC. Updated data on all 55 patients will be available at the time of the presentation. No significant financial relationships to disclose.

A single-arm phase II trial to evaluate the combination of cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (TPF) as induction chemotherapy (IC) in patients (pts) with unresectable SCCHN

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6015-6015 ◽  
Author(s):  
R. Mesia ◽  
S. Vázquez ◽  
J. J. Grau ◽  
J. A. García-Sáenz ◽  
C. Bayona ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Stage Iv ◽  
Stage Design ◽  
Concomitant Boost ◽  
Secondary Neoplasm ◽  
Grade 3 ◽  
Ecog Ps

6015 Background: TPF combination is the new standard IC. Adding cetuximab to PF chemotherapy is superior to PF alone in metastatic disease. We incorporated cetuximab into IC with TPF and subsequent radiotherapy (RT) in unresectable SCCHN. Methods: Phase II trial conducted in 7 Spanish hospitals. Previously untreated pts aged 18–70 yrs, ECOG PS 0–1 with unresectable SCCHN were eligible. Induction comprised T 75mg/m2 day 1, P 75mg/m2 day 1, F 750mg/m2 days 1–5, and cetuximab 250mg/m2 days 1, 8, and 15 (initial dose 400mg/m2 on cycle (C) 1, day 1), repeated every 21 days x 4 C, with prophylactic antibiotics and G-CSF support. Subsequently, pts received accelerated RT with a concomitant boost (69.9Gy) and cetuximab 250mg/m2 weekly. The primary endpoint was the objective response rate (RR) to cetuximab TPF as neoadjuvant therapy. Simon's optimal two-stage design was used to calculate the sample size of 49 evaluable pts. Results: 50 pts were enrolled: median age 54 yrs (33–68); 44 male; all stage IV (T4=31, N2–3=40). Primary sites were: oropharynx, 23; hypopharynx, 16; oral cavity, 5; larynx, 4.41(82%) pts received all 4 cycles of cetuximab TPF; 47 pts received ≥2 C and were evaluable for response using RECIST. 3 pts received <2 C (2 deaths from intercurrent disease and febrile neutropenia, 1 secondary neoplasm diagnosed). The table shows RR. Serious grade 3/4 adverse events (AEs) were: neutropenia 24%; neutropenic fever 20%; infection 6%; thrombocytopenia 4%; diarrhea 12%; hepatotoxicity 4%; hypomagnesemia 2%. Grade 3 AEs were: nausea/vomiting 2%; mucositis 6%; renal failure 4%; asthenia 4%; rash 4%; hypotension 4%. There were 2 AE-related deaths (febrile neutropenia and hepatic insufficiency). Conclusions: The addition of cetuximab to TPF IC in pts with unresectable SCCHN yields a high RR, mainly CR, potentially prolonging survival. Cetuximab TPF combination should be given to pts with good PS with specialized support provided. [Table: see text] [Table: see text]

Phase II study of perioperative chemotherapy with cisplatin (C) and pemetrexed (P) in non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17535-e17535
Author(s):  
Aamer Farooq ◽  
Grace K. Dy ◽  
Todd L. Demmy ◽  
Paul Bogner ◽  
Cynthia Nowadly ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Performance Status ◽  
Bronchopleural Fistula ◽  
Objective Response ◽  
Disease Free Survival ◽  
R0 Resection ◽  
Ecog Performance Status ◽  
N2 Disease

e17535 Background: Pathological complete response (pCR) with neoadjuvant chemotherapy is associated with improved survival in many solid tumors. We evaluated efficacy and tolerability of neoadjuvant plus adjuvant C+P in this phase II trial. Methods: We recruited patients (pts) with clinical stage IB-IIIA (TNM 7th ed) NSCLC, ECOG performance status (PS) 0-1 in this single-arm phase II trial using two-stage design with 90% power to detect pCR rate of >10% (vs null hypothesis of <2%). Pre-treatment mediastinal biopsy was required. Protocol was amended in 2009 to exclude squamous histology. Pts received 3 cycles of C 75mg/m2 + P 500mg/m2 (day 1 every 21 days) followed by surgical resection. Two cycles were delivered adjuvantly within 60-80 days after surgery. The primary end point was pCR. Secondary endpoints were objective response rate (ORR), overall survival (OS), disease-free survival (DFS), and adverse events (AEs). Results: 38 pts were enrolled with median age of 62 yrs, 19 males: 19 females. 74% (N=28) had ECOG PS 0. Preoperatively, 26% (N=10) had squamous histology, 29% (N=11) had biopsy-proven N2 involvement. Median of 4 cycles were administered. ORR was 29% (11 pts with PR). 4 pts did not undergo surgery (3 had disease progression; one became hypoxic during intubation in the OR). Resection status was R2 in 9% (3 of 34 pts), remaining pts had R0 resection. 6 pts had documented N2 clearance; median DFS (mDFS) and OS (mOS) of these pts have not reached (NR) vs 15 and 24 months respectively, in pts with persistent N2 disease. CTC grade 3+ nonhematologic AEs (<10%) include arterial thrombosis, bronchopleural fistula, empyema, hyperglycemia, fatigue and tinnitus. There was no pCR seen and thus accrual to 2nd stage was not pursued. There was no correlation between DFS or OS with ORR or pre-operative stage. There was statistically signification association between DFS with histology (favoring squamous, p=0.03) and post-op stage (p=0.024). The table shows mDFS and mOS in months according to pre-op stage. Conclusions: While the primary endpoint was not met, this regimen is active and well-tolerated perioperatively in NSCLC pts. [Table: see text]

Phase II Trial of Gemcitabine in Refractory or Relapsed Small-Cell Lung Cancer: Eastern Cooperative Oncology Group Trial 1597

2003 ◽  
Vol 21 (8) ◽  
pp. 1550-1555 ◽  
Author(s):  
Gregory A. Masters ◽  
Lieven Declerck ◽  
Charles Blanke ◽  
Alan Sandler ◽  
Russell DeVore ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Ecog Performance Status ◽  
Grade 3

Purpose: Gemcitabine has shown a broad range of activity in solid tumors, including previously untreated small-cell lung cancer (SCLC). The objective of this phase II trial was to investigate the activity of gemcitabine in patients with relapsed SCLC. Patients and Methods: SCLC patients with measurable disease who had experienced treatment failure with one prior chemotherapy regimen were considered eligible. Patients were required to have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and adequate organ function; signed informed consent was also required. Treatment consisted of gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Patients were stratified according to their previous response to first-line chemotherapy (primary refractory v primary sensitive disease). Results: Forty-six patients were enrolled onto this phase II trial (20 refractory and 26 sensitive patients). Forty-two of these patients were assessable for response and survival, and 44 were assessable for toxicity. Median patient age was 60 years, and median ECOG performance status was 1. Principal grade 3/4 hematologic toxicities included neutropenia (27%) and thrombocytopenia (27%). The main grade 3/4 nonhematologic toxicities were pulmonary (9%) and neurologic toxicity (14%). Objective responses occurred in 11.9% of patients overall, including one patient with refractory SCLC (5.6%) and four patients with sensitive SCLC (16.7%). Median survival for the overall group was 7.1 months. Survival was not significantly different for patients with refractory versus sensitive disease. Conclusion: Gemcitabine has modest activity in previously treated SCLC patients. The favorable toxicity profile warrants further investigation, either in combination chemotherapy regimens or with targeted biologic compounds.

Randomized phase II clinical trial comparing tremelimumab (CP-675,206) with best supportive care (BSC) following first-line platinum-based therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8071-8071 ◽  
Author(s):  
P. Zatloukal ◽  
D. S. Heo ◽  
K. Park ◽  
J. Kang ◽  
C. Butts ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Performance Status ◽  
Objective Response ◽  
First Line ◽  
Grade 3

8071 Background: Pts diagnosed with advanced NSCLC with good performance status typically receive platinum-based chemotherapy; however, no approved maintenance therapy exists. Tremelimumab, a fully human anti-CTLA4 mAb, is associated with durable responses in some pts with metastatic melanoma. Methods: This open-label, randomized, multicenter, phase II clinical trial evaluating efficacy and safety of tremelimumab as maintenance therapy was conducted in pts with locally advanced or metastatic NSCLC with ECOG performance status ≤1. Pts treated with ≥4 cycles of first-line platinum-based therapy resulting in either stable disease (SD) or response per RECIST were eligible and were randomized 3–6 weeks after prior therapy. Pts received 15 mg/kg IV tremelimumab Q90D or BSC until disease progression. Primary endpoint was progression-free survival (PFS) at 3 months. Secondary endpoints included safety, objective response rate, and 1-year survival. Results: Eighty-seven pts received tremelimumab (n=44) or BSC (n=43). Nine (20.9%; 90% CI: 11.4%, 33.7%) pts receiving tremelimumab and 6 (14.3%; 90% CI: 6.4%, 26.3%) pts receiving BSC were progression free at 3 months. Among pts receiving tremelimumab, there were 2 (4.8%) partial responses and 7 (16.6%) SDs, compared with 0 and 6 (14.3%) pts receiving BSC, respectively. Treatment-related adverse events (AEs) were observed in 27 (61.4%) pts receiving tremelimumab and 3 (7.0%) receiving BSC. Nine pts (20.5%) receiving tremelimumab reported grade 3 or 4 AEs compared with 0 patients receiving BSC. The most common grade 3 or 4 AEs attributed to tremelimumab were diarrhea and colitis (n=4, 9.1%). Conclusions: In pts with advanced NSCLC and good performance status receiving platinum-based first-line therapy, single-agent tremelimumab was tolerable, with safety consistent with prior studies. Although PFS analysis did not demonstrate superiority of tremelimumab over BSC, the 4.8% objective response rate seen only in the investigational arm may support future combination studies. Analysis of 1-year survival is forthcoming. [Table: see text]

Sorafenib plus cisplatin and gemcitabine in the treatment of advanced hepatocellular carcinoma (HCC): A phase II study by the Gruppo Oncologico dell'Italia Meridionale (prot. GOIM 2705).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 225-225 ◽  
Author(s):  
F. Giuliani ◽  
A. Febbraro ◽  
R. Addeo ◽  
D. Rizzi ◽  
E. Maiello ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Treatment ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Hepatic Function ◽  
Tumor Control ◽  
Advanced Hepatocellular Carcinoma ◽  
Ecog Performance Status ◽  
Advanced Hcc ◽  
Written Informed Consent

225 Background: Sorafenib is the standard treatment in advanced HCC. The combination of cisplatin and gemcitabine demonstrated to be active and well tolerated in tumors with a similar poor outcome such as pancreatic and biliary-tract cancers. Considering these data, the GOIM started a phase II trial aiming to evaluate the activity and safety of the combination of sorafenib, gemcitabine and cisplatin in advanced HCC. Methods: Patients affected by advanced HCC, not suitable for surgery or locoregional procedures, with measurable disease (Recist criteria), age ≥ 18 years, clip-score ≤3, ECOG performance status ≥ 60 (K.fsky), adequate bone marrow reserve and renal and hepatic function and who signed written informed consent, were enrolled and received cisplatin 40 mg/mq iv plus gemcitabine 800 mg/mq iv bi-weekly, while sorafenib was orally administrated at the dosage of 400 mg bid continuously. A maximum of 6 cycles of chemotherapy was planned; a maintenance with sorafenib was permitted for not progressing patients. The evaluation of activity was performed every three cycles. A Simon's two stage, two steps study design was applied: at the first step, at least 3 OR had to be observed among the first 28 patients to continue the enrollment. Up to now, 23 patients have been enrolled. Their main characteristics were: sex (male/female) 19/4, median age: 70 yrs, median PS 80,main sites of disease liver 22, lymph nodes 4, lung 2, others 3. Results: Up to now 18 patients are evaluable for activity while 5 are too early. One CR, 3 PR, 6 SD and 8 PRO for an ORR of 4/18 (22%) and a tumor control of 10/18 (55%). Twenty-one patients are evaluable for safety. The main observed side effects (%G1-2/G3-4) (NCI criteria) were: hand-foot skin reaction (HFSR) 9/14, mucositis 9/4, diarrhea 23/4, nausea/vomiting 23/0, leucopenia 23/0, anemia 9/0, thrombocytopenia 19/4, asthenia 14/14, cardiovascular 0/4, others 9/4. Conclusions: Our preliminary data seems to demonstrate that the combination of cisplatin, gemcitabine, and sorafenib is active and well tolerated in advanced HCC patients. The accrual is ongoing. No significant financial relationships to disclose.

Phase II study of combination therapy with docetaxel, cisplatin, and S-1 (DCS) for advanced gastric cancer: (KDOG 0601)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4555-4555
Author(s):  
N. Nakayama ◽  
W. Koizumi ◽  
T. Sasaki ◽  
S. Tanabe ◽  
K. Nishimura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
High Response Rate ◽  
Ecog Performance Status ◽  
Eligibility Criteria

4555 Background: Our previous phase I study (Oncology 2008, 75:1–7) provided evidence that combination chemotherapy with docetaxel, cisplatin, and S-1 (DCS) is effective and well tolerated in patients with advanced gastric cancer. The present multicenter phase II study was conducted to confirm the efficacy and toxicity of DCS in advanced gastric cancer. Methods: Eligibility criteria included a histologically proved diagnosis of gastric adenocarcinoma with at least one measurable metastatic lesion, no previous treatment for gastric cancer except for surgery, an ECOG performance status of 0 to 2, and adequate organ function. Docetaxel (40 mg/m2) and cisplatin (70–60 mg/m2) were given intravenously on day 1, and S-1 was given orally at a dose of 40 mg/m2 twice daily from days 1 to day 14 of a 28-day cycle. Patients received a maximum of 6 cycles. Subsequently, patients were given repeated cycles of S-1 plus docetaxel (DS). The primary endpoint was the objective response rate. Results: 59 patients (47 men, 12 women) were enrolled. The median age was 62 (range: 35–75) years. PS 0/1/2 was 40/18/1. The median number of treatment cycles was 7 (DCS 6+DS 1: range, 1–20). Because myeloid suppression and renal dysfunction developed during the study, we lowered the recommended dose of cisplatin from 70 mg/m2 to 60 mg/m2. The dose of cisplatin was 70 mg/m2 in 19 patients and 60 mg/m2 in 40. The overall response rate was 81.3% (48/59; 95% CI, 80.7–91.2). The response rates with cisplatin 70 mg/m2 and 60 mg/m2 were 78.9% (95% CI, 60.5–97.2) and 82.5% (95% CI, 70.7–94.2), respectively. Tumor down-staging was achieved in 9 (18.7%) of the 48 patients who responded to treatment. The median survival time and median progression-free survival were not reached. Grade 3 or 4 major toxicity comprised leukopenia (44.0%), neutropenia (72.8%), anemia (15.2%), febrile neutropenia (13.5%), anorexia (6.7%), nausea (5.1%), vomiting (5.1%), fatigue (1.6%), and diarrhea (5.1%). There was one treatment-related death caused by the perforation of the primary tumor. This patient refused surgery. Conclusions: DCS was a well-tolerated regimen with a high response rate in patients with advanced gastric cancer. Cisplatin at a dose of 60 mg/m2 was considered adequately effective. No significant financial relationships to disclose.

Phase II study of dasatinib in the treatment of head and neck squamous cell carcinoma (HNSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6022-6022 ◽  
Author(s):  
H. D. Brooks ◽  
B. Glisson ◽  
C. Lu ◽  
A. Sabichi ◽  
F. Johnson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Open Label ◽  
Ecog Performance Status ◽  
Open Label Phase ◽  
Grade 3 ◽  
Efficacy Parameters

6022 Background: Dasatinib is a potent inhibitor of src-family kinases, ephA2, PDGFR, Abl, and c-kit. A single-center, open-label, phase II trial was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of dasatinib in recurrent or metastatic HNSCC. Methods: Pts with measurable disease by RECIST, who received 0 or 1 prior regimen for recurrent or metastatic HNSCC with an ECOG performance status 0–1 and tumor tissue appropriate for IHC and FISH were eligible. Dasatinib 100 mg bid was given for 28-day cycles. Primary endpoints were 12-wk progression-free survival (PFS) and objective response rate (ORR). Pts who took at least 1 dose of dasatinib and who died or left study before 12 wks were counted as progressive disease (PD). A 2 stage design, closure after accrual of 15 pts was required if PFS was 45% or less and ORR was 0. Otherwise, planned accrual was 35. Response was assessed at 4 and 12 wks. PK was studied in pts receiving dasatinib per PEG. Biomarkers relevant to Src pathway were planned in tissue and blood. Results: Fifteen pts were accrued. To date, 13 pts are evaluable for response, and 15 pts for toxicity. No grade 3/4 hematologic toxicities were noted. Grade 2–4 nonhematologic toxicities(n): pleural effusion(2), nausea/vomiting(2), dehydration(1), diarrhea(1), dyspnea(1). Toxicity led to hospitalization of 4 pts and drug discontinuation in 5 pts. ORR was 0. One pt was stable at 12 wks (PFS: 7.6%). This pt stopped drug at 15 wks due to toxicity, but also had PD. One pt died on study and cause was deemed unlikely related. Conclusions: Dosed at 100mg bid, dasatinib led to a characteristic toxicity profile in this pt population. Rates of hospitalization and discontinuation for toxicity were fairly high. Final efficacy parameters are pending evaluation of 2 pts. Evaluation of PK and tissue/blood biomarkers is ongoing. No significant financial relationships to disclose.

A phase II study of capecitabine, irinotecan, and bevacizumab (XELIRI-A) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15019-e15019
Author(s):  
E. X. Chen ◽  
S. Welch ◽  
M. Krzyzanowska ◽  
H. MacKay ◽  
J. Knox ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Ecog Performance Status ◽  
Optimal Dosing ◽  
Open Label Phase ◽  
Dosing Strategies ◽  
Grade 3 ◽  
Ecog Ps

e15019 Background: Capecitabine (XEL), irinotecan (IRI) and bevacizumab (A) are all active agents in the treatment of mCRC. However, combining these agents has proven to be problematic due to overlapping toxicities. Optimal dosing strategies for this combination remain unclear. This study prospectively evaluated toxicity and efficacy of the XELIRI-A combination with dose modification. Methods: This was a single-institution, open-label phase II clinical trial. Eligible pts include those with previously untreated metastatic CRC, adequate organ function and ECOG performance status 0–2. IRI (200 mg / m2) and A (7.5 mg / kg) were given on day 1, and XEL (1000 mg / m2 p.o. BID) was given on days 1–14 of every 21-day cycle. The dose of XEL was reduced to 750 mg / m2 BID for pts age ≥ 65. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, time to progression, overall survival and toxicity. Results: 50 pts (ECOG PS 0:1 = 27:23; male:female= 34:16) were enrolled over 19 months. Median age was 58 (range: 35–72). 7 pts had prior adjuvant chemotherapy. A total of 360 cycles were administered, with a median of 6 (range: 1–16). To date, 20 confirmed PR, 3 unconfirmed PR, and 20 SD by RECIST criteria were observed (ORR= 40%, disease control rate 86%). The median PFS was 11.1 months (95% CI: 9.2 months - not reached), and the 1-year progression-free rate was 49%. 7 pts have gone on to have metastatectomy. The most frequently reported related grade 3 or 4 adverse events were neutropenia (6), hand-foot syndrome (6), and diarrhea (5). One death was seen on study, and 1 pt had treatment-emergent grade 3 hypertension. Conclusions: XELIRI-A at doses studied appears to be well- tolerated. Results are favorable compared to those from previous studies. XELIRI-A at reduced doses is safe and effective as first-line treatment for mCRC. [Table: see text]

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