Phase II study of combining immunotherapy and pulsed low dose rate radiotherapy for abdominal metastasis of gastric cancer.

e16099 Background: Immune-mediated responses against tumor antigens by checkpoint inhibitors (CPIs) may be enhanced by radiotherapy and the combination may hold therapeutic promise. Pulsed low dose rate radiotherapy (PLDR) is an effective strategy for abdominal tumor by taking advantage of low dose hyper-radiosensitivity with maximizing tumor response and minimizing adverse events by radiotherapy. In this phase II study, we prospectively analyzed the response and adverse events of the combination strategy of CPIs and PLDR for abdominal metastasis of gastric cancer. Methods: Eligibility criteria included pathologically confirmed advanced gastric adenocarcinoma with abdominal metastasis. Patients received XELOX regimen chemotherapy, anti-PD-1 toripalimab, and PLDR for abdominal metastasis, prescription dose was 50-56Gy/25-28f. The primary endpoint was objective response rate (ORR) and safety. Secondary endpoints were regional response rate (RRR) and regional controlled rate (RCR) for radiotherapy target tumor, progression-free survival (PFS), and overall survival (OS). Results: Between November 2018 and June 2020, 24 patients were enrolled and included in the efficacy analysis. 13 of them were first line therapy, and 11 of them were second line therapy. The ORR was 70.8% and the combination regimen were tolerable. The RRR was 83.3% and the RCR was 95.8%. The median PFS was 11.1 months and the median OS was not yet reached. Conclusions: In this phase II clinical trial, the combination of Immunotherapy and radiotherapy provided good response and toleration for abdominal metastasis of gastric cancer. It suggested clinical efficacy of this regimen in patients with advanced gastric cancer. Clinical trial information: NCT03061162.

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A combination chemotherapy of weekly paclitaxel and doxifluridine (5’-DFUR: an intermediate metabolite of capecitabine) in patients with unresectable or recurrent gastric cancer in an outpatient setting. Final results of a multicenter phase II trial

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15050 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15050-15050

Author(s):

S. Yoshino ◽

T. Nishimura ◽

S. Hazama ◽

M. Oka ◽

H. Ozasa ◽

...

Keyword(s):

Gastric Cancer ◽

Adverse Events ◽

Phase Ii ◽

Response Rate ◽

Performance Status ◽

Single Agent ◽

Outpatient Setting ◽

Eligibility Criteria ◽

Line Therapy ◽

Recurrent Gastric Cancer

15050 Background: Paclitaxel (PTX) and 5’-DFUR have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between PTX and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. We conducted a combination phase II study of PTX and 5’-DFUR in patients with unresectable or recurrent gastric cancer to evaluate the efficacy and safety in an outpatient. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer who had measurable lesions fitting RECIST, up to one prior chemotherapy, a performance status of 0–2 and adequate organ function. According to our results of phase I study (Proc ASCO 2004, Abstr. 4228), the treatment included PTX 70 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and 5’-DFUR 600 mg/body p.o. everyday until there was disease progression or the appearance of unacceptable toxicity. Primary endpoint was: RR; and secondary endpoints were OS, PFS, TTF and onset rate of adverse events. Results: Between June 2004 and July 2006, 42 patients were enrolled in this study: including 34 men; 8 women; median age of 70 years (range, 44–85 years); and PS levels were, zero with 27, one with 13 and two with 2 patients. In 42 eligible patients, clinical usefulness was evaluated resulting in response rate of 40.5% (CR, 1; PR, 16; SD, 17; PD, 6; and NE, 2 patients). The first-line therapy involved 28 patients in whom the response rate was 50.0%. The second-line therapy involved 13 patients (all TS-1 failure) in whom the response rate was 23.1%. OS was 371 days, PFS was 170 days and TTF was 147 days. All patients were treated in outpatient. Severe adverse events were found in 2 patients to discontinue the present treatment, though other adverse events were relatively mild without death due to the present therapy. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), appetite loss (4.8%), neuropathy (4.8%), and fatigue (4.8%). Conclusions: The outpatient combination of a weekly PTX and 5’-DFUR chemotherapy is active and well tolerated. No significant financial relationships to disclose.

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Multi-center, phase II study for combination therapy with paclitaxel/doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1: Final results (OGSG 0302)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15025 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15025-15025

Author(s):

H. Takiuchi ◽

H. Imamura ◽

M. Imano ◽

Y. Kimura ◽

H. Ishida ◽

...

Keyword(s):

Gastric Cancer ◽

Combination Therapy ◽

Adverse Events ◽

Phase Ii ◽

Response Rate ◽

Phase Ii Study ◽

High Reliability ◽

Initial Time ◽

Present Treatment ◽

Recurrent Gastric Cancer

15025 Background: We report here results of phase II study for a combination therapy with paclitaxel/doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1. S-1 is an oral fluoropyrimidine drug that combines tegafur, CDHP, and oxonic acid (Oxo), which has been most frequently used in Japan. Methods: Subject registration was started to employ 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to RECIST, and with resistant to S-1 treatment (PS, 0–2; and patient’s ages ranged from over 20 to under 75 years). We employed dosages that Hyodo et. al. used in phase I study and recommended as a standard regimen including paclitaxel, 80 mg/m2, i.v. on days 1 and 8; and doxifluridine, 600 mg/m2, p.o. on days 1–14.. These were repeated every 3 weeks. Primary endpoint of present phase II study was: RR; and secondary endpoints were OS, PFS, and onset rate of adverse events. Results: From September, 2003 to March, 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49–75 years); and PS levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except 2, clinical usefulness was evaluated resulting in response rate of 18.2% (PR, 6; SD, 15; PD, 10; and NE, 2 patients). OS was 321 days, and PFS was 119 days. Severe adverse events were found in 3 patients to discontinue the present treatment though; other adverse events were relatively mild without no death due to the present therapy. Conclusions: Patients in the present study with advanced/recurrent gastric cancer were those resistant to S-1 treatment. Response rate was 18.2% increasing to 63.6% when SD was added. OS resulted in relatively long period of 321 days, while OS from initial time starting S-1 treatment was 619 days. This suggests that the present treatment is useful as the sequential therapy. Adverse events were controllable suggesting a high reliability of the present therapy. In conclusion, the present therapy with paclitaxel/doxifluridine could be a treatment of choice as an useful second line chemotherapy for patients undergone S-1 treatment. No significant financial relationships to disclose.

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A phase II trial of low-dose nab-paclitaxel for patients with previously treated or recurrent advanced gastric cancer (OGSG1302).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.350 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 350-350

Author(s):

Masashi Hirota ◽

Shigeyuki Tamura ◽

Hirokazu Taniguchi ◽

Atsushi Takeno ◽

Hiroshi Imamura ◽

...

Keyword(s):

Gastric Cancer ◽

Peripheral Neuropathy ◽

Adverse Events ◽

Phase Ii ◽

Low Dose ◽

Response Rate ◽

Phase Ii Trial ◽

Dose Intensity ◽

Relative Dose Intensity ◽

Grade 3

350 Background: Paclitaxel is a key drug in second-line chemotherapy for advanced or recurrent gastric cancer (AGC) and nanoparticle albumin-bound paclitaxel (nab-PTX) is also widely used in Japan. A previous phase II trial in Japan showed the effectiveness of nab-PTX (260 mg/m2) administered every 3 weeks (q3w) in patients with AGC with a response rate (RR) of 27.8%; however, toxicity was major concern with grade ≥3 neutropenia (49.1%) and peripheral neuropathy (23.6%). To solve this problem, we investigated the efficacy and safety of low-dose q3w nab-PTX regimen in AGC. Methods: Eligibility requirements included: aged ≥20 years, HER2-negative, histologically confirmed, unresectable or recurrent gastric adenocarcinoma, one or more prior chemotherapy containing fluoropyrimidine regimens, presence of measurable lesion(s) according to RECIST ver. 1.1, ECOG PS of 0–2, and adequate organ function. Nab-PTX was administered at a dose of 220 mg/m2 every 3 weeks. The primary endpoint was the RR. Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease-control rate (DCR), incidence of adverse events, relative dose intensity and proportion of patients who received subsequent chemotherapy. Results: Thirty-three patients were enrolled from 10 institutions in Japan. Of the 32 patients treated with protocol therapy, RR (CR, PR) was 3.1% (95% CI, 0–16.2%), which was not reached the protocol-specified threshold (p = 0.966). DCR (CR, PR, SD) was 37.5% (95% CI, 21.1–56.3%), median OS and PFS were 6.3 months (95% CI, 4.4–14.2) and 2.2 months (95% CI, 1.8-3.1). Relative dose intensity was 97.8% (215 mg/m2). 62.5% of patients received subsequent chemotherapy. Most common grade ≥3 adverse events were neutropenia (38%), anemia (13%), fatigue (19%), anorexia (16%), and peripheral neuropathy (13%). Conclusions: Low-dose regimen of q3w nab-PTX was slightly less toxic, although it did not demonstrate the same effect as the original regimen in response rate. Therefore, it is not recommended for AGC in second or later line setting. Clinical trial information: UMIN 000012701.

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A phase II study of oxaliplatin with low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced gastric cancer

Acta Oncologica ◽

10.1080/02841860600791483 ◽

2007 ◽

Vol 46 (3) ◽

pp. 336-341 ◽

Cited By ~ 23

Author(s):

Sung Yong Oh ◽

Hyuk-Chan Kwon ◽

Bong-Gun Seo ◽

Sung-Hyun Kim ◽

Jae-Seok Kim ◽

...

Keyword(s):

Gastric Cancer ◽

Continuous Infusion ◽

Advanced Gastric Cancer ◽

Phase Ii ◽

Low Dose ◽

Phase Ii Study ◽

First Line ◽

First Line Therapy ◽

Line Therapy

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Phase II Study of WEE1 Inhibitor AZD1775 Plus Carboplatin in Patients With TP53-Mutated Ovarian Cancer Refractory or Resistant to First-Line Therapy Within 3 Months

Journal of Clinical Oncology ◽

10.1200/jco.2016.67.5942 ◽

2016 ◽

Vol 34 (36) ◽

pp. 4354-4361 ◽

Cited By ~ 96

Author(s):

Suzanne Leijen ◽

Robin M.J.M. van Geel ◽

Gabe S. Sonke ◽

Daphne de Jong ◽

Efraim H. Rosenberg ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Adverse Events ◽

Phase Ii ◽

Overall Response Rate ◽

Response Rate ◽

Phase Ii Study ◽

First Line ◽

First Line Therapy ◽

Line Therapy

Purpose AZD1775 is a first-in-class, potent, and selective inhibitor of WEE1 with proof of chemopotentiation in p53-deficient tumors in preclinical models. In a phase I study, the maximum tolerated dose of AZD1775 in combination with carboplatin demonstrated target engagement. We conducted a proof-of-principle phase II study in patients with p53 tumor suppressor gene ( TP53)–mutated ovarian cancer refractory or resistant (< 3 months) to first-line platinum-based therapy to determine overall response rate, progression-free and overall survival, pharmacokinetics, and modulation of phosphorylated cyclin-dependent kinase (CDK1) in skin biopsies. Patients and Methods Patients were treated with carboplatin (area under the curve, 5 mg/mL⋅min) combined with AZD1775 225 mg orally twice daily over 2.5 days every 21-day cycle until disease progression. Results AZD1775 plus carboplatin demonstrated manageable toxicity; fatigue (87%), nausea (78%), thrombocytopenia (70%), diarrhea (70%), and vomiting (48%) were the most common adverse events. The most frequent grade 3 or 4 adverse events were thrombocytopenia (48%) and neutropenia (37%). Of 24 patients enrolled, 21 patients were evaluable for efficacy end points. The overall response rate was 43% (95% CI, 22% to 66%), including one patient (5%) with a prolonged complete response. Median progression-free and overall survival times were 5.3 months (95% CI, 2.3 to 9.0 months) and 12.6 months (95% CI, 4.9 to 19.7), respectively, with two patients with ongoing response for more than 31 and 42 months at data cutoff. Conclusion To our knowledge, this is the first report providing clinical proof that AZD1775 enhances carboplatin efficacy in TP53-mutated tumors. The encouraging antitumor activity observed in patients with TP53-mutated ovarian cancer who were refractory or resistant (< 3 months) to first-line therapy warrants further development.

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