Phase I study of pemetrexed plus cisplatin in unresectable, advanced gastric carcinoma in Taiwan

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14009-14009
Author(s):  
J. Chen ◽  
Y. Chao ◽  
L. Chen ◽  
C. Li ◽  
W. Reece ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Recommended Dose ◽  
Ecog Performance Status ◽  
Advanced Gastric Carcinoma ◽  
Post Surgery ◽  
Number Of Patients ◽  
Grade 3

14009 Background: Phase I of this Phase I/II study (H3E-AA-S038) was conducted to determine the recommended dose of pemetrexed (PT) when given with cisplatin (Cis) to patients with unresectable, advanced gastric carcinoma. Methods: Patients 18 to 70 years of age, with stage IV disease or post-surgery recurrence, no prior palliative chemotherapy, and an ECOG performance status of 0 or 1 were included. Patients received PT and Cis on Day 1 every 21 days. Cis was dosed at 75 mg/m2. PT dosage was planned at 600, 700, 800, and 900 mg/m2. Vitamin B12 and folic acid supplementation, and dexamethasone (or equivalent corticosteroid) prophylaxis were required. The initial number of patients to be enrolled per dose level (DL) was 3. If 0/3 patients had dose-limiting toxicity (DLT), PT dose was escalated. If 1/3 patients had DLT, 3 more patients were enrolled at that DL. If ≥2 patients had DLT, the dose was not escalated further. The recommended dose of PT for Phase II was the highest dose at which <2/6 patients experienced DLT. The following toxicities were defined as DLT: death due to toxicity; neutropenia [<0/5 × 109/L for ≥5 days, or <1.0 × 109/L with fever (≥38.5 ºC)]; thrombocytopenia (<10.0 × 109/L, or <50.0 × 109/L with bleeding); AST or ALT >20 × ULN; and non-hematological toxicities of CTC grade 3 or 4 (except nausea and vomiting). Intra-patient dose escalation was not permitted. Results: Sixteen patients were enrolled. The mean (±SD) age of enrolled patients was 52.8 (±10.0) years, and the majority were male (62.5%). At DL1, 0/3 patients experienced DLT. At DL2, 1/6 patients had DLT. At DL3, 3/7 patients had DLT, and so PT dose was not escalated. All DLTs occurred in cycle 1; 2 involved neutropenia, 1 tumor hemorrhage, and 1 hypokalemia. Grade 3/4 toxicities were experienced by 12/16 (75%) patients, including 9 (56%) hematological and 10 (63%) non-hematological events. Five out of thirteen (38%) patients with measurable disease had a RECIST response (2 had a complete response, 1 each at DL1 and DL2; 3 had a partial response, 2 at DL2 and 1 at DL3). At this interim analysis, 2 patients were still on therapy. Conclusions: The recommended dose of PT is 700 mg/m2. Phase II will examine response and safety of PT plus Cis in advanced gastric carcinoma. [Table: see text]

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2

2019 ◽  
Vol 37 (3) ◽  
pp. 230-238 ◽  
Author(s):  
Teresa Macarulla ◽  
Roberto Pazo-Cid ◽  
Carmen Guillén-Ponce ◽  
Rafael López ◽  
Ruth Vera ◽  
...  
Keyword(s):  
Phase I ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Ductal Adenocarcinoma ◽  
Tolerability Profile ◽  
Ecog Performance Status ◽  
Actuarial Survival ◽  
Number Of Patients

Purpose Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS. Patients and Methods In the phase I part of this study, patients were randomly assigned to one of the following four parallel GA treatment arms (six patients per arm): a biweekly schedule of NAB-paclitaxel (150 mg/m2 [arm A] or 125 mg/m2 [arm C]) plus gemcitabine 1,000 mg/m2 or a standard schedule of 3 weeks on and 1 week off of NAB-paclitaxel (100 mg/m2 [arm B] or 125 mg/m2 [arm D]) plus gemcitabine 1,000 mg/m2. The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study, the primary end point of which was 6-month actuarial survival. Results Arms B and D were selected for the phase II part of the study. A total of 221 patients (111 patients in arm B and 110 patients in arm D) were enrolled. Baseline characteristics including median age (71 and 68 years in arms B and D, respectively), sex (51% and 55% men in arms B and D, respectively), and metastatic disease (88% and 84% in arms B and D, respectively) were comparable between arms. The most frequent grade 3 or 4 toxicities in arms B and D were anemia (12% and 7%, respectively), neutropenia (32% and 30%, respectively), thrombocytopenia (7% and 11%, respectively), asthenia (14% and 16%, respectively), and neurotoxicity (11% and 16%, respectively). In arms B and D, there were no significant differences in response rate (24% and 28%, respectively), median progression-free survival (5.7 and 6.7 months, respectively), and 6-month overall survival (63% and 69%, respectively). Conclusion NAB-paclitaxel administered at either 100 and 125 mg/m2 in combination with gemcitabine on days 1, 8, and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS.

Phase I results of the randomized, placebo controlled, phase I/II study of the novel oral c-Met inhibitor, ARQ 197, irinotecan (CPT-11), and cetuximab (C) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) who have received front-line systemic therapy.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 527-527 ◽  
Author(s):  
C. Eng ◽  
J. C. Bendell ◽  
A. Bessudo ◽  
N. Y. Gabrail ◽  
J. Diamond ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Response ◽  
Ecog Performance Status ◽  
Tumor Cell Migration ◽  
Arq 197 ◽  
Grade 3

527 Background: ARQ 197 selectively inhibits the c-Met receptor tyrosine kinase (RTK), which has been implicated in tumor cell migration, invasion, proliferation, and angiogenesis. CPT-11 plus C is a standard of care for CPT-11-refractory mCRC pts with WT KRAS tumors. Resistance to C has been associated with activation of alternative RTK pathways including c-Met. We hypothesize that adding ARQ 197 to CPT-11 plus C may decrease resistance to C therapy and improve pt outcomes. Methods: The primary objectives of phase I were to evaluate safety and tolerability of ARQ 197 administered in combination with CPT-11 plus C, and to define a recommended phase II dose (RPTD). Pts with surgically unresectable locally advanced or mCRC who received at least 1 prior line of chemotherapy, KRAS WT and ECOG performance status < 2 were eligible. Cohorts of 3 pts each were treated with CPT-11 (180 mg/m2) and C (500 mg/m2) every 2 weeks along with escalating doses of ARQ 197 (120, 240, 360 mg) PO BID. Blood and tissue were collected for PK, biomarker, and other analyses. If no DLTs were observed during the first 28-day cycle in 3 pts treated in cohort 3, 360 mg BID would be defined as the RPTD. Responses were assessed every 8 weeks per RECIST v1.1. Results: Nine pts were treated in 3 cohorts. Median age: 53 yrs (range 30-77); ECOG PS 0/1: 4/5; median prior therapies: 2 (range 1-4). No DLTs were observed. The RPTD for ARQ 197 was 360 mg BID. To date, two pts have discontinued (1 disease progression and 1 withdrew consent after achieving complete response) and 7 pts remain on study. The reported grade 3/4 adverse events were: neutropenia (3/4: 1/1), and one case each of grade 3 fatigue, leucopenia, acneiform rash, vomiting, anemia and syncope. Preliminary efficacy data in 9 evaluable pts include 1 CR (after 4 cycles), 2 PR (after 2 cycles), 5 SD, and 1 PD as best response. Conclusions: The combination of ARQ 197 and CPT-11 plus C was well tolerated with encouraging preliminary antitumor activity. The RPTD for ARQ 197 was 360 mg BID. The randomized phase II portion of the study continues accrual. [Table: see text]

Dasatinib plus capecitabine (Cap) for progressive advanced breast cancer (ABC): Phase I study CA180004

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1012-1012
Author(s):  
G. Somlo ◽  
F. Atzori ◽  
L. Strauss ◽  
A. Rybicki ◽  
X. Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Combined Treatment ◽  
Breast Cancer Cell Lines ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Study Laboratory

1012 Background: SRC family kinases (SFK) mediate numerous signal-transduction pathways relevant to breast cancer as well as osteoclast function. Dasatinib, a potent oral inhibitor of SFK and other kinases has preclinical activity in breast models and in vitro synergy with Cap in some breast cancer cell lines (KPL-4 and HCC-70). A phase I trial of dasatinib plus Cap was conducted to define dose-limiting toxicities (DLT), maximum tolerated (MTD), and recommended phase II (RP2D) doses. Methods: Sequential cohorts of pts with ABC were treated with Cap twice daily (BID) on days 1–14 and dasatinib daily in 21-day cycles using dose levels (DL) for Cap (mg/m2) and dasatinib (mg): DL1: Cap 825 + dasatinib 50 BID; DL2: Cap 825 + dasatinib 70 BID; DL3: Cap 1000 + dasatinib 70 BID; DL3a: Cap 1000 + dasatinib 100 once daily (QD). All pts had ECOG performance status 0–1, had prior anthracycline and/or taxane, and received ≤2 regimens in advanced setting. MTD was based on DLT in first cycle and RP2D also based on tolerability of additional cycles. Results: 31 pts with ABC, median age 53 years (range 36–78) were treated. Number of pts treated/evaluable for DLT/reported DLT (event) were DL1: 7/6/1 (headache, grade 3); DL2: 9/7/0; DL3: 6/6/1 (diarrhea, grade 3), and DL3a: 9/9/1 (pneumonia, grade 3). Most frequent AEs related to either drug and occurring at any time on study (n pts) were nausea (12), vomiting (7), diarrhea (6), abdominal pain (2), fatigue (8), headache (7), musculoskeletal pain (1), and pleural effusion (4); hand-foot syndrome (5) was as expected for Cap alone. 11 patients experienced a Grade 3–4 non-hematologic AE at some point during the study. Laboratory abnormalities were uncommon. To date, 20 pts have continued treatment for ≥6 weeks and 9 pts for ≥12 weeks. Number of pts who (at any time) reduced dasatinib/reduced Cap/discontinued for toxicity were DL1: 2/2/1; DL2 2/2/3; DL3: 2/1/2; DL3a: 0/1/1. Updated safety and efficacy data will be presented. Conclusions: Dasatinib + Cap was tolerated without unexpected combined-treatment toxicity; few pts required dose reduction in later cycles. The recommended phase II dose, Cap 1000 plus dasatinib 100 QD, is well tolerated and will be studied for efficacy in an expanded patient cohort. [Table: see text]

A phase I/II study of S-1 plus cisplatin alternating with S-1 plus docetaxel in patients with advanced gastric cancer (AGC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 101-101
Author(s):  
A. Hosokawa ◽  
K. Ogawa ◽  
S. Kajiura ◽  
Y. Tsukioka ◽  
T. Kobayashi ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Survival Data ◽  
Performance Status ◽  
Maximum Tolerated Dose ◽  
First Line ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Starting Dose ◽  
Grade 3

101 Background: S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with AGC in Japan, and S- 1 plus docetaxel showed promising results for AGC in clinical trials. To investigate the usefulness of S-1 plus cisplatin alternating with S-1 plus docetaxel as first-line treatment in patients with AGC, we conducted a phase I/II study to determine the maximum tolerated dose (MTD), the recommended dose (RD), preliminary efficacy and toxicity. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 74, ECOG performance status (PS) of 0 to 2; adequate organ function; and written informed consent. Cisplatin was administered on day1 and the dose was escalated by 10 mg/m2 from starting dose of 40 mg/m2 in phase I part. S-1 was given orally at 80 mg/m2 on day1-14. Docetaxel was administered at 40 mg/m2 on day 22 in combination with S-1 80 mg/m2 on days 22-35. The treatment was repeated every 6 weeks. The RD was studied in every 3-6 patients cohort and determined according to the pre-defined DLTs. Primary endpoint of phase II was the response rate (RR). Results: Between Aug 2006 and Jul 2010, 33 pts were enrolled. Nine patients entered the phase I part and 24 enrolled in phase II part. In the phase I part, the MTD of cisplatin was presumed to be 50 mg/m2, because 50% of patients (3/6) developed DLTs. Therefore, the RD of cisplatin was estimated as 40 mg/m2, and the 27 patients received the treatment at RD level. Patients characteristics were as follows: median age=65 years (range 48-74), Male: female=21:6, PS 0:1:2=11:16:0, diffuse: intestinal=19:8, initially unresectable: recurrent=24:3. The RR was 59.2% (95% CI, 40.7-77.7). Median follow-up period was 14.6 months, median PFS was 7.9 months, and median survival time was 17.2 months, although survival data remain to be confirmed. Major grade 3/4 toxicities were neutropenia (63%), leucopenia (41%), and anemia (33%). These toxicities were tolerable and manageable. No treatment-related death was observed. The updated analysis will be presented at the meeting. Conclusions: This alternating treatment seems to be effective and well tolerated in the first-line treatments in patients with AGC. No significant financial relationships to disclose.

scholarly journals Beneficial Treatment Management with Trifluridine/Tipiracil in a Patient with Metastatic Colorectal Cancer and Pronounced Hematological Event History during Previous Treatments

2018 ◽  
Vol 11 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Volker Kaechele ◽  
Jürgen Hess ◽  
Wolfgang Schneider-Kappus
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Performance Status ◽  
Recommended Dose ◽  
Hematological Toxicity ◽  
Ecog Performance Status ◽  
History Of ◽  
Grade 3

Trifluridine/tipiracil (FTD/TPI) significantly improves overall survival in patients with metastatic colorectal cancer (mCRC). The most common treatment-related event (grade ≥3) was hematological toxicity. We here report long-term disease-stabilizing FTD/TPI treatment of an mCRC patient (KRAS wild-type, ECOG performance status 1 at baseline and at the end of FTD/TPI therapy) with multifocal synchronous metastases and a longstanding history of extensive hematological events during previous treatments. Finally, this 62-year-old male patient was treated for 10 months with FTD/TPI by consecutive alteration of treatment parameters: (i) initial daily dose reduction to 80 mg (72% of the recommended dose), (ii) 20 days dose delay, (iii) a second and later third dose reduction to 70 mg and 60 mg (about 64% and 55%, respectively, of the recommended dose), and (iv) 30 µg per day of granulocyte colony-stimulating factor administration first for 3 days, and later for 5 days, for each treatment cycle.

Combination of Oxaliplatin Plus Irinotecan in Patients With Gastrointestinal Tumors: Results of Two Independent Phase I Studies With Pharmacokinetics

1999 ◽  
Vol 17 (6) ◽  
pp. 1751-1751 ◽  
Author(s):  
Ernesto Wasserman ◽  
Caroline Cuvier ◽  
François Lokiec ◽  
François Goldwasser ◽  
Salima Kalla ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Maximum Tolerated Dose ◽  
Two Phase ◽  
Phase I Studies ◽  
Phase Ii Studies ◽  
Minute Period ◽  
Grade 3 ◽  
Febrile Episodes

PURPOSE: Two phase I studies of the oxaliplatin and irinotecan combination were performed in advanced gastrointestinal cancer patients to characterize the safety and pharmacokinetics of the regimen. PATIENTS AND METHODS: Patients with a performance status (PS) of ≤2 and normal hematologic, hepatic, and renal functions received oxaliplatin (2-hour intravenous infusion) followed 1 hour later by irinotecan administered over a 30-minute period, every 3 weeks. Dose levels that were explored ranged from 85 to 110 mg/m2 for oxaliplatin and 150 to 250 mg/m2 for irinotecan. Plasma pharmacokinetics of total and ultrafiltrable platinum, irinotecan, SN-38, and its glucuronide, SN-38G, were determined. RESULTS: Thirty-nine patients with gastrointestinal carcinomas (24 with colorectal cancer [CRC], four with pancreas cancer, four with gastric cancer, three with hepatocarcinoma, and four with other) received 216 treatment cycles. Median age was 54 years (range, 21 to 72 years); 95% had PS of 0 to 1; all but six had failed fluorouracil (5-FU) chemotherapy. The maximum-tolerated dose was oxaliplatin 110 mg/m2 plus irinotecan 200 mg/m2 in one study and oxaliplatin 110 mg/m2 plus irinotecan 250 mg/m2 in the other study. Grade 3 to 4 diarrhea and febrile neutropenia were dose-limiting toxicities; other toxicities included emesis and dose-cumulative neuropathy. Recommended dose for phase II studies is oxaliplatin 85 mg/m2 and irinotecan 200 mg/m2. At this dose (12 patients, 65 cycles), grade 3 and 4 toxicities per patient included the following: emesis in 42% of patients, neutropenia in 33% (febrile episodes in 17%), peripheral neuropathy in 25%, delayed diarrhea in 17%, and thrombocytopenia in 8%. Two patients with Gilbert's syndrome experienced severe irinotecan toxicity. No plasmatic pharmacokinetic interactions were detected. Seven partial responses were observed in 24 CRC patients. CONCLUSION: This combination is feasible, with activity in 5-FU–resistant CRC patients. Phase I studies that explore the every-2-weeks schedule, in addition to phase II studies of this schedule (as well as in combination with 5-FU) as second-line therapy of metastatic CRC, are ongoing.

Dasatinib Has Activity in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL/SLL), a Phase II Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3162-3162 ◽  
Author(s):  
Philip C. Amrein ◽  
Eyal Attar ◽  
Tak Takvorian ◽  
Ephraim Hochberg ◽  
Karen K. Ballen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase Ii ◽  
Performance Status ◽  
Lymphocytic Leukemia ◽  
Ct Scans ◽  
Fish Analysis ◽  
Ecog Performance Status ◽  
Bone Marrow Biopsies ◽  
Lyn Kinase ◽  
Grade 3

Abstract Background: Preclinical studies have shown that CLL cells overexpress lyn kinase protein, and in vitro inhibition of lyn kinase leads to apoptosis of the CLL cells (Contri, J Clin Invest 2005). Because dasatinib has been shown to inhibit lyn kinase in CML cells at concentrations easily achievable in patients, we undertook this phase II study in patients with previously treated CLL/SLL. Methods: Patients were required to be over 18 years of age, have a diagnosis of CLL/SLL by flow cytometry or immunohistochemistry, and have failed either 1 course of treatment with a fludarabine-containing regimen or 2 non-fludarabine containing regimens. The starting dose of dasatinib was 140 mg daily by mouth. This dose could be reduced to 100 mg or 80 mg daily for toxicity. At baseline all patients had bone marrow biopsies and CT scans, and these were repeated at 2 months. Sequential blood and bone marrow samples were tested for lyn kinase activity. Results: Among the 15 patients enrolled there were 10 male and 5 female subjects with a median age of 59 years (40–78 years). ECOG performance status was 0 in 9 subjects, 1 in 3, and 2 in 3 subjects. All patients had previously received fludarabine, and 5 patients required treatment within 6 months of their last regimen. The median number of prior treatments was 3 (range: 1 to 7). By cytogenetic/FISH analysis there were 5 patients with del(17p) and 6 patients with del(11q). All patients required treatment by NCI–WG criteria. The major toxicity encountered was myelosuppression: grade 3 + 4 neutropenia in 10 subjects, grade 3 + 4 thrombocytopenia in 4 subjects. Gastrointestinal toxicity was minor with only 1 subject experiencing grade 3 diarrhea. Other toxicities: 1 patient had a grade 2 pleural effusion, 1 patient had a transient serum K=9.9 (likely an artifact of high white count and without clinical sequelae), and 1 patient had a transiently prolonged QTc of 516 ms. There were no fatal events, and all toxicities were reversible. The median duration on study was 10 weeks, but 5 responding or stable patients have remained on treatment for over 9 months. Partial responses (PR) by NCI-WG criteria were achieved in 2 of the 15 patients (13% with 90% CI 2%–36%). An additional 2 patients would have qualified for PR (lasting &gt;2 months) except for myelosuppression. Among the remaining 11 patients, 6 had nodal responses (2 CR and 4 PR) by physical exam (PE) without a 50% reduction in lymphocytosis. CT scans confirmed nodal responses in 3 of the 10 patients with nodal responses by PE. The relationship between clinical response and lyn kinase, bcl-2, and mcl-1 expression will be presented at the meeting. Conclusions: Dasatinib has modest activity in CLL, and combinations with standard agents, perhaps in an intermittent schedule, should be considered in subsequent trials.

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.

A phase II trial of gemcitabine, docetaxel, and bevacizumab (GDB) in metastatic pancreas cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4606-4606
Author(s):  
V. J. Picozzi ◽  
L. A. Canlas ◽  
P. L. Sicuro ◽  
T. W. Malpass
Keyword(s):  
Tumor Marker ◽  
Disease Progression ◽  
Phase Ii ◽  
Pancreas Cancer ◽  
Performance Status ◽  
Bleeding Events ◽  
Ecog Performance Status ◽  
Ca 19.9 ◽  
Secondary Endpoints ◽  
Grade 3

4606 Background: Metastatic pancreas cancer (MPC) remains identified with poor outcome. Benchmark response statistics in MPC include response rate (RR) 20–30%, time to disease progression (TTP) 3.5–5.5 mo, median overall survival (OS) 6–9 mo and 1- year (yr) OS 20–30%. At our center, adding docetaxel (D) to G in MPC produced 6.0 mo TTP and 10.5 mo OS (Jacobs et.al. Canc Invest 2004). As bevacizumab (B) added to combination chemotherapy has produced major improvement in OS for other cancers (e.g. colon cancer), we chose to study the GDB regimen in MPC. Methods: Our study was phase II, single-phase. Eligiblity criteria included 1) diagnosis of MPC, 2) chemotherapy naivity, 3) ECOG performance status 0 /1, 4) organ function adequate for therapy. Therapy included G 1000 mg/m2 IV bolus, D 40 mg/m2 IV and B 10 mg/kg IV every 2 weeks (wks) for 1 yr unless disease progression or prohibitive treatment toxicity occurred. Patients were radiographically restaged every 8 wks. Primary endpoint was TTP. Secondary endpoints included therapy toxicity, radiographic RR (RECIST criteria), tumor marker RR (CA 19.9) and OS. Results: Of 27 enrolled patients (pts), 25 pts are currently evaluable for response, 24 pts for TTP. Median age is 58 yrs. Primary metastatic disease sites were liver (n=18), peritoneum ( n=6), lymph node ( n=2) and lung (n=1). 7/27 pts (26%) experienced grade 3 or higher treatment-related toxicity, including pulmonary (n=3), neutropenia (n=3), bleeding events (n=3), VTE (n=2), hypertension (n=1), hypokalemia (n=1) and skin rash (n=1). 1 pt died from respiratory failure, possibly therapy-related. To date, disease control at 8 wks is 100% (24/24 pts) radiographic RR is 48% (12/25 pts) and tumor marker RR is 95% (18/19 evaluable pts expressed CA19.9, median decline 80%, 5 pts normalized) . Of 24 pts evaluable for TTP, 9/18 (50%) initial pts achieved > 9 mo TTP (range 9.2–18.5 mo); the remaining 6 pts continue progression-free on therapy (range 2+-7+ mo). Median OS has not been reached and will be > 8.3 mo. Response data will be updated at the meeting. Conclusions: 1) The GDB regimen is overall well-tolerated; pulmonary toxicity was the major therapy-related toxicity concern. 2) GDB is significantly active in MPC as witnessed by response rates achieved. 3) Further study of the GDB regimen in MPC is warranted. [Table: see text]

Final results of phase I and pharmacokinetic study of SJG-136 administered on a daily x 5 schedule

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13506-e13506 ◽  
Author(s):  
T. M. Kadia ◽  
S. Faderl ◽  
Z. Estrov ◽  
M. Konopleva ◽  
S. George ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Performance Status ◽  
Median Number ◽  
Clinical Activity ◽  
Vascular Leak ◽  
Ecog Performance Status ◽  
Acute Leukemias ◽  
Number Of Patients ◽  
Dose Levels

e13506 Background: SJG-136 is a pyrrolobenzodiazepine dimer that forms covalent DNA crosslinks in a sequence-specific manner in the minor groove. In vitro testing demonstrated a broad pattern of antitumor activity in sub-nmol concentrations. A phase I study in patients (pts) with solid tumors revealed clinical activity, defined MTD as 30 mg/m2/d administered on daily x 3 schedule, and confirmed manageable toxicity. Here we report the results of a CTEP-sponsored phase I trial of SJG-136 administered on a daily x 5 schedule in pts with relapsed or refractory (R/R) leukemias. Methods: Previously treated pts with R/R acute leukemias (AML, ALL, high risk MDS, CML blast phase) or R/R CLL with adequate organ function and ECOG performance status of ≤ 2 were eligible for the study. The starting dose level was 6 mcg/m2 given intravenously daily x 5 days on a 21 day cycle. Pts were sequentially enrolled in cohorts of 3 and the dose was escalated in a classic 3+3 schema at the dose levels: 6, 12, 24, and 36 mcg/m2. Repeat courses and intrapatient dose escalation were allowed. Results: Sixteen pts (11M, 5 F) were enrolled on the study. The median age of the patients was 53 (21–84). Thirteen (81%) pts had R/R AML, and 3 (19%) had R/R ALL of which 5 (31%) had diploid and 6 (38%) had adverse cytogenetics. Median number of prior therapies was 3 (2–6). Pts enrolled at each dose level (mcg/m2) were: 6 (3 pts), 12 (5 pts), 24 (4 pts), 36 (4 pts). The median number of cycles delivered was 1 (0–5). The dose of 36 mcg/m2 was found to be above the MTD, with the DLT being grade 3 soft tissue edema. Other manifestations of vascular leak including grade I, II hypoalbuminemia, edema, and pleural effusions were seen in a number of patients starting at dose level 24 mcg/m2 and above. Other non-dose limiting toxicities included nausea, dyspnea, fatigue, bloating, and insomnia. One pt had a PR, 8 pts had stable disease, and 6 had progression. Pharmacokinetic characteristics in this population will be reported. Conclusions: SJG-136 is safe and active in patients with advanced leukemias. Edema and other vascular leak syndromes are characteristic toxicities of the agent at higher dose levels. 24 mcg/m2 is the recommended phase II dose for the daily x 5 schedule. No significant financial relationships to disclose.

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