Randomised prospective phase II study of combination chemotherapy epidoxorubicin, cisplatin, 5-FU (ECF) versus epidoxorubicin, cisplatin, capecitabin (ECX) in patients with advanced or metastatic gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4571-4571
Author(s):  
J. Ocvirk ◽  
M. Rebersek ◽  
E. Skof
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Central Venous Access ◽  
Performance Status ◽  
Infusion Pump ◽  
Metastatic Gastric Cancer ◽  
Venous Access ◽  
Ecog Performance Status ◽  
Indwelling Catheter ◽  
Phase Ii Studies

4571 Background: In phase II studies ECF with 5- FU inf. resulted in response rates (RR) > 50 %. Despite high responses the potential drawback of ECF may be the poor patient’s (pts) acceptability of the indwelling catheter and external infusion pump and related complications: sepsis, catheter-related infections, shoulder pain, thrombosis and pneumothorax. Capecitabin can maintain a constant level of 5- FU without complications and inconvenience associated with central venous access. The aim was to compare the efficacy and safety ECF versus ECX. Secondary endpoint was overall survival. Methods: Pts with histological proven, previously untreated advanced or metastatic gastric cancer, >18 years, ECOG performance status 0- 2 and adequate organ and hematological function were randomized to ECF or ECX. In ECF epidoxorubicin 50 mg/m2 and cisplatin 60 mg/m2 were administrated on day 1 by i.v., 5- FU 200 mg/m2/day was administrated by cont. inf. day 1- 14 of each cycle. Cycle was repeated every 3 weeks. In ECX epidoxorubicin 50 mg/m2 and cisplatin 60 mg/m2 were administrated on day 1 by i.v., capecitabin 825 mg/m2 twd was administrated orally day 1- 14. Cycle was repeated every 3 weeks. Results: Seventy- one pts were enrolled in this study between Jan 03 to Dec 05. Male 80 %, median age 56 yrs (40- 77). Thirty pts received ECF and 41 pts received ECX . All pts were assessable for responses and toxicity. The overall clinical RR were 45 % including 12.9 % partial responses (PR) and 6.4 % complete responses (CR) in ECF group and 69 % including 21.4 % PR and 4.7 % CR in ECX group. Median OS and TTP were 8.8 months (mos) ± 7.8 and 6.0 mos ± 4.4 in ECF group and 10.5 mos ± 7.2 and 7.0 mos ± 4.6 in ECX group respectively. The most frequent grade ¾ side effects graded according to CTCAE - 3 were fatigue - 20 % in ECF group and 19.5 % in ECX group, hematological (neutropenia) - 16 % in ECF group and 4.8 % in ECX group, nausea - 10 % in ECF group and 7.3 % in ECX group, diarrhea - 2.4 % in ECX group, hand- foot syndrome - 2.4 % in ECX group. Conclusions: ECX is at least effective as ECF with less toxic pattern and more convenient for pts and could replace ECF in first- line therapy in pts with advanced or metastatic gastric cancer. No significant financial relationships to disclose.

Phase II study of irinotecan, 5-fluorouracil (5-FU) and leucovorin combination chemotherapy in taxane and cisplatin-based chemotherapy-refractory metastatic gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15599-e15599
Author(s):  
J. Yoon ◽  
S. Cho ◽  
W. Bae ◽  
J. Hwang ◽  
H. Shim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study ◽  
Performance Status ◽  
Haematological Toxicity ◽  
Metastatic Gastric Cancer ◽  
High Dose ◽  
Ecog Performance Status ◽  
Grade 3

e15599 Background: The role of the second line chemotherapy in advanced gastric cancer was not clear, but possibility of prolongation of survival is open question. Irinotecan is promising agents in gastric cancer and this phase II study evaluated the efficacy and safety of combination chemotherapy with irinotecan, high dose of 5-fluorouracil (5-FU) and leucovorin in taxane and cisplatin based chemotherapy refractory metastatic gastric cancer. Methods: Eligible criteria were as followed; histologic confirmed adenocarcinoma of stomach, previously treated with taxane and cisplatin, age≥18, Eastern Clinical Oncology Group (ECOG) performance status of 1 or less, adequate organ function. Irinotecan (150 mg/m2) as a 30-min infusion and leucovorin (200 mg/m2) as a 15-min infusion were given on day 1, followed by 5-FU 400 mg/m2bolus infusion then 5-FU 2,400 mg/m2 as a 48-hour continuous infusion. This cycle was repeated every 2 weeks until disease progression or unacceptable toxicities. Results: Thirty-four patients were enrolled. The median age was 57 years (range 27–73 years), and the ECOG performance status of all patients was 1. All patients were evaluable for safety and survival and twenty seven patients (79.4%) were evaluable for tumor response. The overall response rate was 18.5% (95% CI: 3.9–33.1). The median progression free survival and overall survival were 4.6 (95% CI: 2.4–6.9) and 9.3 months (95% CI: 5.2–13.4), respectively. Greater than grade 3 haematological toxicities were neutropenia in nine (26.5%), febrile neutropenia in one (2.9%) and thrombocytopenia in one patient (2.9%). The major non-haematological toxicity was asthenia, but most of patients showed grade 1 or 2. Greater than grade 3 non- haematological toxicities were elevated AST/ALT in four (11.8%), hyperbilirubinemia in two (5.9%), nausea in two patients (5.9%). Conclusions: This results showed that the combination chemotherapy with irinotecan, 5-FU and leucovorin was well tolerated and active in taxane and cisplatin refractory patients. No significant financial relationships to disclose.

scholarly journals A Review of Docetaxel: Its Use in the Treatment of Gastric Cancer

2010 ◽  
Vol 2 ◽  
pp. CMT.S5191
Author(s):  
Alessandro Inno ◽  
Michele Basso ◽  
Alessandra Cassano ◽  
Carlo Barone
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Phase Ii Studies ◽  
Combination Regimens

Docetaxel, a member of the taxane family, promotes cell death by binding β-tubulin and has demonstrated activity against several human malignancies, both as a single agent and in combination therapy. It has been approved in Europe and the US as front-line treatment for advanced gastric cancer in combination with cisplatin and fluorouracil (DCF regimen). This approval was based on the results of a pivotal study (V325) which demonstrated that the addition of docetaxel to the reference regimen of cisplatin and fluorouracil improves overall survival and progression-free survival with a better quality of life despite increased toxicity (mainly haematological). Modifications of DCF regimen have been successfully investigated as a means of making the treatment more tolerable and suitable also for elderly patients or patients with poor performance status. Emerging data from several phase II studies suggest that other docetaxel-based combination regimens with anthracyclines or irinotecan have interesting activity with acceptable toxicity profiles, but the true efficacy of these regimens needs to be assessed in large randomized phase III studies. Thus, the best docetaxel-containing regimen has yet to be identified. Docetaxel also represents a good candidate for combination with novel molecular target agents. In light of the high response rates observed in phase II-III studies, a docetaxel-based chemotherapy regimen might also be considered a treatment option as perioperative or adjuvant therapy in potentially curable gastric cancer and further studies with or without biological agents are eagerly awaited in this setting.

Phase II study of S-1 and biweekly docetaxel combination in advanced or recurrent gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14031-14031
Author(s):  
Y. Kakeji ◽  
E. Oki ◽  
K. Nishida ◽  
T. Koga ◽  
E. Tokunaga ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Metastatic Gastric Cancer ◽  
Preclinical Study ◽  
Current Phase ◽  
Tumor Control ◽  
Recurrent Gastric Cancer ◽  
Grade 3

14031 Background: Docetaxel (TXT) and S-1 are active agents against gastric cancer. A synergistic antitumor effect has been shown in a preclinical study (Takahashi et al., Oncology 2005), and our previous phase I trial demonstrated the safety and tolerability of the combination, and its potent activity. To prospectively evaluate toxicity and efficacy of S-1/ biweekly TXT, we conducted the current phase II study in patients with advanced and recurrent gastric cancer. Methods: Patients (pts) with advanced or recurrent gastric cancer, who have not received any chemotherapy except postoperative chemotherapy (not including S-1 or TXT), were eligible for the trial, and were treated with docetaxel 35 mg/m2 one hour iv infusion on day 1 and 15, and S-1 at a full dose of 80 mg/m2/day for two weeks every four weeks. Results: Thirty-five pts with measurable lesions (RECIST) (10 females, 25 males; performance status [PS] 0/1/2: 23/8/4, age 27–74, differentiated/undifferentiated adenocarcinoma: 19/16) have been enrolled. A total of 113 cycles were administered (median 3, range 1–6), and all pts were assessable for toxicity and efficacy. Grade 3–4 toxicities were: neutropenia in 20.0% (grade 4: 11.4%) of patients, leukocytopenia in 11.4% (grade 4: 0%), anemia in 5.7%, appetite loss in 8.6%, stomatitis in 8.6%, fever in 2.9%, and fatigue in 2.9%. All treatment related toxicities resolved, and no toxic death was reported. Thirteen partial responses (PR) were obtained, resulting in an overall response (OR) rate of 37.1% (95% CI: 0.22–0.55). Thirteen pts (37.5%) had stable disease, and 4 pts (12.5%) progressed. The tumor control rate was 74.3% (95% CI: 0.57–0.88). The median survival time (MST) and time to treatment failure (TTF) were 326 and 75 days, respectively. Conclusions: The combination of S-1/ biweekly TXT is active in advanced or recurrent gastric cancer, and can be given safely with proper management of adverse events even in outpatient clinic. S-1/ biweekly TXT is one of the most effective regimen to control metastatic gastric cancer with less toxicity. No significant financial relationships to disclose.

A phase I study of S-1 in combination with sorafenib in metastatic renal cell carcinoma (mRCC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 447-447
Author(s):  
Seiichiro Ozono ◽  
Tatsuya Takayama ◽  
Masato Fujisawa ◽  
Hideaki Miyake ◽  
Katsuyoshi Hashine ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Phase Ii ◽  
Performance Status ◽  
Previous Treatment ◽  
Japanese Patients ◽  
Maximum Tolerated Dose ◽  
Ecog Performance Status ◽  
Phase Ii Studies ◽  
History Of ◽  
Level 2

447 Background: S-1 is an oral anticancer agent combining tegafur, a prodrug of 5-fluorouracil, with 5-chloro-2,4-dihydroxypyridine and potassium oxonate. The purpose of this study was to confirm the recommended dose (RD) and maximum tolerated dose (MTD) of S-1 in combination with sorafenib, a small molecular inhibitor of several tyrosine protein kinase, in Japanese patients with mRCC. We assessed dose-limiting toxicities (DLTs) and pharmacokinetic interactions during the first cycle of treatment. Methods: Eligible patients had a histologically confirmed diagnosis of clear cell or papillary mRCC, measurable lesions, a history of no previous treatment or not more than 1 regimen of cytokine treatment, an ECOG performance status of 0 or 1, prior nephrectomy, and adequate organ functions. In this study, four dose levels were prepared, and the starting dose was set at Level 1B. S-1 was administered on days 1 to 28, and sorafenib was given on days 1 to 42 as one cycle. The MTD was assessed using a “3 + 3” dose escalation design and was defined as the highest dose level for which the incidence of DLTs was less than 33%. Results: Between August 2009 and March 2010, 9 patients were enrolled. Two DLTs occurred in patients assigned to level 2, which was the full therapeutic dose of each agent. Therefore, the MTD was not confirmed, but the RD was determined to be level 2. Although renal clearance affected the pharmacokinetics of S-1, there were no obvious drug interactions between S-1 and sorafenib. Details are shown in the Table. Conclusions: This combination therapy can be administered with acceptable tolerability, no overlapping toxicity, and no drug interactions. The RD for phase II studies was fixed at level 2, and a phase II study is ongoing. [Table: see text]

PD-L1 expression in patients with metastatic gastric cancer in South Korea.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1571-1571
Author(s):  
Hyo Song Kim ◽  
Ting Wu ◽  
Hyunki Kim ◽  
Hyun Cheol Chung ◽  
Jaffer A. Ajani ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
South Korea ◽  
Tumor Cells ◽  
Performance Status ◽  
Metastatic Gastric Cancer ◽  
Rank Test ◽  
Cancer Center ◽  
Immune Gene ◽  
Ecog Performance Status ◽  
Percentage Survival

1571 Background: Data are limited and conflicting regarding programmed death ligand 1 (PD-L1) expression as prognostic of clinical outcomes in patients (pts) with metastatic gastric cancer (mGC) treated with standard of care (SOC). Factors affecting the association between PD-L1 expression and outcomes include type of assay and antibody, scoring system for PD-L1 expression, and method of tissue collection. We analyzed the association between tumor PD-L1 expression and clinical parameters in Korean pts with inoperable mGC. Methods: A retrospective study was performed in 201 pts with inoperable mGC from Yonsei Cancer Center in Seoul, South Korea. Biopsy samples were collected at diagnosis. Tumor PD-L1 expression was measured by IHC using the 22C3 PD-L1 antibody pharmDx kit (Dako North America, Carpinteria, CA, USA). PD-L1 positivity was defined as a combined positive score (CPS) of ≥1%, where CPS is PD-L1+ cells (tumor cells, macrophages, lymphocytes) over the total number of tumor cells, expressed as a percentage. Survival was analyzed using Kaplan-Meier methods, log-rank test, and Cox proportional hazards models, adjusting for age, sex, and ECOG performance status. Results: A total of 189/201 (94%) pts received chemotherapy as SOC and were included in this analysis. Median age was 56 years (range, 21-82), 37% of pts were women, and 28% had a BMI ≥24. All pts had stage IV metastatic disease and 27%, 49%, and 24% had well to moderately differentiated, poorly differentiated, and signet ring cell tumors, respectively. Prevalence of PD-L1 positivity was 72.5%. PD-L1 positivity was not associated with age, BMI, or histologic grade. Median overall survival (OS) for the PD-L1+ and PD-L1– groups was 10.9 and 10.2 months, respectively ( P= 0.92). The hazard ratio for the PD-L1+ vs the PD-L1–group was 1.02 (95% CI, 0.74-1.39) before adjusting for age, sex, and ECOG performance status and 1.08 (95% CI, 0.77-1.51) after adjusting. Conclusions: Based on this preliminary assay and cutoff, results suggest that PD-L1 expression is not a prognostic factor for mGC. Additional biomarker analyses (eg, immune gene expression profile and microsatellite instability) are planned.

Final results of a phase II trial of bexarotene capsules as 3rd or subsequent line therapy in patients with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7099-7099
Author(s):  
R. Govindan ◽  
J. Crowley ◽  
L. Schwartzberg ◽  
P. Kennedy ◽  
C. Williams ◽  
...  
Keyword(s):  
Skin Rash ◽  
Phase Ii ◽  
Performance Status ◽  
Lipid Lowering ◽  
Ecog Performance Status ◽  
Phase Ii Studies ◽  
Heavily Pretreated ◽  
Adequate Organ Function ◽  
Apoptotic Effects

7099 Background: Bexarotene, a rexinoid that binds to RXR nuclear receptors, has antiproliferative, differentiating, and apoptotic effects. Phase II studies of bexarotene plus chemotherapy in previously untreated NSCLC suggested improved patient survival. This study evaluated bexarotene for relapsed advanced NSCLC. Methods: Patients were eligible if they had NSCLC Stage IIIB wet/IV, had failed ≥ 2 prior systemic therapies, had previously received a taxane and platinum, had ECOG performance status (PS) 0–2, and had adequate organ function. Bexarotene 400 mg/m2 daily plus prophylactic levothyroxine and a lipid-lowering agent were given until disease progression or unacceptable toxicities occurred. The primary efficacy endpoint was survival. To detect a 50% increase in median survival from 4 months, as shown with 3rd line chemotherapy, to 6 months, 125 evaluable patients were required for a 90% power at a 1-sided 5% significance. Results: A total of 146 patients were enrolled at 32 sites. Median age = 66 (range, 34–87), male = 51%, PS 2 = 23%, adenocarcinoma = 54%, and median prior therapies = 3 (range 1–7) with 55% having failed gefitinib. Bexarotene was usually well tolerated and there were no therapy-related deaths. For the 124 patients who were treated for at least 14 days and were considered evaluable for efficacy, median and 1-year survival were 6 months and 25%, respectively. Baseline albumin < 3 g/dL and PS = 2 were significantly associated with shorter survival. For 26 patients who developed hypertriglyceridemia plus skin rash by Day 21, median and 1-year survival were 12 months and 44%, respectively, vs. 2 months and 12% in 36 patients with neither (p = 0.0003). Partial response was reported in 1 patient. When assessed by FACT-G, quality of life was improved or stabilized in 65% of patients. Conclusions: Survival of patients with heavily pretreated NSCLC may be extended with oral bexarotene therapy. Confirmation of these results with a randomized trial is warranted. Ongoing investigations attempt to explain the notable outcome reported in this and other bexarotene trials in the subset of patients who developed hypertriglyceridemia with or without skin rash. [Table: see text]

Phase II study of a combination of S-1 and weekly paclitaxel in patient with advanced or recurrent gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14033-14033
Author(s):  
Y. Ueda ◽  
H. Yamagishi ◽  
D. Ichikawa ◽  
J. Morii ◽  
N. Kakihara ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Weekly Paclitaxel ◽  
Tumor Control ◽  
Ecog Performance Status ◽  
Standard Regimen ◽  
Highly Active ◽  
Recurrent Gastric Cancer

14033 Background: Based on the results of our phase I study on a combination of S-1 (tegafur, oxonic acid, and CDHP) and weekly paclitaxel (PTX) for advanced or recurrent gastric cancer (ARGC) (Ueda et al, ASCO 2004), we conducted a multi-center phase II study to prospectively evaluate efficacy, QOL, and toxicity of S-1 plus weekly PTX in patients with ARGC. Methods: Eligibility included patients with histologically-proven ARGC, 20–80 years old, having a ECOG performance status (PS) of 0–2 and adequate organ functions, and having received no prior chemotherapy except postoperative adjuvant therapies without taxanes. S-1 was given orally at a dose of 80 mg/m2/day for 14 consecutive days (days 1–14) followed by a 2-week rest. PTX was administered weekly as a 1-hour intravenous infusion on days 1, 8, and 15. This treatment was repeated every 4-weeks as one cycle. Results: Fifty-four patients with measurable lesions (RECIST) were enrolled between Feb. 2004 and Nov. 2005. Histologically, a half of the patients had differentiated type and the other patients had undifferentiated type adenocarcinoma. The median age was 61 (range, 38–78). Three-fourths were male patients. The PS was 0/1/2 in 47/6/1 patients respectively. Thirty nine were primary cases and 15 were recurrent cases after gastrectomy. Treatment was terminated in two patients for toxicities and in one patient for refusal during the first cycle; thus compliance of 94.4%. A total of 254 cycles were administered (median 4.7, range 2–14), and 45 patients were assessable efficacy and toxicity until Dec. 2005. In these 45 assessable patients, 2 CRs and 27 PRs were obtained, resulting in an overall response rate of 64.4%. Twelve pts (26.7%) had stable disease, and 4 pts (8.9%) progressed. The tumor control rate was 91.1%. Conclusions: The combination of S-1 and weekly PTX is highly active for ARGC, and can be given safely with good tolerance and convenience profile. It is a candidate for the standard regimen and expected to contribute to better prognosis and QOL in ARGC patients. 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.

Preliminary Phase II Results of SGN-30 (Anti-CD30 Monoclonal Antibody) in Patients with Cutaneous Anaplastic Large Cell Lymphoma (ALCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4802-4802 ◽  
Author(s):  
Madeleine Duvic ◽  
Joy Kunishige ◽  
Youn H. Kim ◽  
Andres Foreno-Torres ◽  
Lauren C. Pinter-Brown ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Adverse Events ◽  
Phase Ii ◽  
Systemic Therapy ◽  
Performance Status ◽  
Objective Response ◽  
Study Drug ◽  
Large Cell ◽  
Ecog Performance Status ◽  
Phase Ii Studies

Abstract Background: SGN-30 is a chimeric monoclonal antibody (mAb) directed against the CD30 antigen which is expressed on Hodgkins and non Hodgkins Lymphoma. SGN-30 has been well tolerated in phase I and phase II studies and objective responses have been seen in systemic ALCL. Methods: Adult CD30 positive cutaneous ALCL patients who have progressed after treatment with radiotherapy and/or systemic therapy, ECOG performance status 0–2, are treated in a multicenter, single arm phase II study. SGN-30 at 4 mg/kg is administered by IV infusion monthly for a maximum of 6 consecutive doses. Evaluation of response (Physician’s Global Assessment) is performed 3–4 weeks after each infusion. In the absence of an objective response after two doses, patients may receive SGN-30 at 12 mg/kg for the remaining infusions. Results: Patient Characteristics: 5 patients (4 male, 1 female) with median age 63 years (range 42–79) have been enrolled. Median number of prior therapies is 3 (range 1–4). All patients had at least 1 prior systemic therapy, and 3 of 5 patients (60%) had received at least two of the following therapies: Targretin, CHOP, or radiotherapy. 4 patients received 6 doses of SGN-30; of these 1 patient increased to 12 mg/kg at dose 3, 1 at dose 5, and 2 at dose 2. One patient received a single 4 mg/kg dose. Efficacy: 4 of 5 patients (80%) achieved a response; 1 CR and 3 PR (2 designated as “Marked Improvement” and 1 as “Almost Clear”). The patient with a CR had a history of Mycosis Fungoides and developed CD30+ ALCL. He had complete resolution of trunk lesions after 5 doses of SGN-30, received one additional dose of SGN-30, and maintained a durable CR of > 40 days. Of the 3 patients with PR, 1 attained a response after one dose, and 2 after 3 doses. One patient with concurrent LyP received a single dose of SGN-30 9 days after discontinuing methotrexate, experienced a worsening of his disease, and came off the study with PD. Tolerability: The most common adverse events in the 5 patients included pedal edema, arthralgia, and insomnia, each of which occurred in 2 patients. Of the 6 grade 3/4 adverse events, 4 were considered to be unrelated to SGN-30, and the relationship of 2 were unknown (pruritis and increased number of lesions). There was 1 SAE, an 80 year old male hospitalized with pneumonia after 6 doses of SGN-30 died on study of myocardial infarction secondary to aortic stenosis, considered unrelated to study drug. Conclusions: Preliminary data indicate the drug is well tolerated and shows antitumor activity. Recruitment into the study continues.

A phase I study of sequential administration of S-1 and cisplatin (CDDP) for patients with metastatic gastric cancer (MGC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14101-14101
Author(s):  
E. Baba ◽  
H. Fujishima ◽  
H. Kusaba ◽  
T. Esaki ◽  
H. Ariyama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Performance Status ◽  
Metastatic Gastric Cancer ◽  
Sequential Administration ◽  
Grade 3

14101 Background: The combination of 5-FU and CDDP has been reported to be active against metastatic gastric cancer (MGC), and great synergy has been shown in vivo and in vitro when 5-FU precedes CDDP. We investigated a sequential combination of S-1 (Tegafur, oxonic acid, CDHP) followed by CDDP for MGC. Methods: In order to determine a maximum tolerated dose (MTD) and recommended phase II dose (RD), we conducted a phase I trial applying increasing doses of oral administration of S-1 (65–80mg/m2) for 21 days and increasing doses of CDDP (60–80mg/m2) on day 22 every 35 days. Pts with metastatic or recurrent gastric cancer, no prior chemotherapy, measurable disease, performance status ECOG less than 3, and adequate organ functions were eligible for the study. Three pts were treated at each dose level with escalation based on toxicity. Fifteen pts were included and evaluated for DLT and MTD. Results: DLT was NCICTC grade 3 anorexia and fatigue in patients treated at the dose level 5 of S-1 80mg/m2 and CDDP 80mg/m2. Other toxicity more than grade 3 was neutropenia (grade 3) and nausea/vomiting (grade 3). Non-hematological toxicities were grade 1/2 and included diarrhea, nausea and stomatitis. There was no treatment-related mortality. The recommended dose was a combination of S-1 80mg/m2 and CDDP 70mg/m2. A tentative median survival was 19.5 months. Conclusions: This sequential S-1 and CDDP administered every 35 days is tolerable and beneficial for patients with MGC, and thus the consequent phase II trial is recommended. A multicenter phase II study is currently under way. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document