A study of the combination of oxaliplatin, capecitabine, and herceptin (trastuzumab) and chemoradiotherapy in the adjuvant setting in operated patients with HER2+ gastric or gastro-esophageal junction cancer (TOXAG study).

Abstract

TPS182 Background: Trastuzumab in combination with chemotherapy has been shown to prolong survival of HER2+ esophago-gastric cancer patients. The primary aim of our study was to evaluate safety and tolerability of trastuzumab (T) in combination with oxaliplatine (O), capecitabine (C) and radiation (R) therapy in the adjuvant setting in curatively resected esophago-gastric cancer patients. Methods: Forty patients with IB or higher stages was planned to be recruited and here we report the interim analyses on 22. We would consider the study positive if at least 64.4% of patients could tolerate the therapy. Eligible patients received T 8 mg/kg intravenously (iv) on Day 1 of cycle 1 and 6 mg/kg iv on day 1 of every following 3-weekly cycle for 1 year as 17 cycles, with O 100 mg/m2 iv on Day 1 of cycles 1-3 and C 850 mg/m2 orally twice daily on days 1-14 of cycles 1-3 and on 5 days per week during chemo-radiotherapy. R was given at a total dose of 45 Gy divided into 25 doses on 5 treatment days per week for 5 weeks starting from the 1st day of cycle 4. Results The median age was 57.5 years (Min-Max: 35-74). Of 22 patients; 15 were male (68.2%), 21 (95.5%) had an ECOG PS score ≤ 1, 21 (95.5%) had D2 lymph node resection. There were 11 serious adverse events. Two patients died on therapy; 1 secondary to pulmonary thrombo-emboli, and the other had to cerebral ischemia (thought to be due to Behçet’s disease), and 7 died of progression. There were 6 dose reductions (1 for T, 2 for O and 3 for C), T was stopped in 1 patient, C was interrupted 8 times (mostly during radiotherapy). Patients who have completed 3 cycles of O, C, T and 4th and 5th cycles of chemo-radiation therapy with C and T were defined as tolerable. Out of 22 patients, 19 (86.4%) were tolerable (Chi Square test: p = 0.0623). Median survival time for interim analysis patients (n = 22) was 22 months (95% CI: 11-23 months). Conclusion T in combination with O, C and chemo-radiation with C and T was tolerable with the tolerability rate of 86.4%, in curatively resected HER2 + esophago-gastric cancer adjuvant treatment. Clinical trial information: NCT01748773.

Early diagnosis of breast cancer from exhaled breath by gas chromatography‐mass spectrometry (GC/MS) analysis: A prospective cohort study

“…The overexpression of human epidermal growth factor receptor 2 (HER2, c‐erbB2) is found in up to 30% of breast cancers; in addition, compared to patients with HER2‐negative breast cancer, patients with HER2‐positive breast cancer were associated with significantly worse outcomes 51 . Many studies have demonstrated that HER2 is also present in other cancers, particularly in gastric cancer 52‐55 . Trastuzumab is a critical drug for the treatment of HER2‐positive breast cancer that also has been shown to be useful for the treatment of HER2‐positive gastric cancer 56 ; it is approved by the European Union, the United States, and China for the treatment of gastric cancer.…”

“…51 Many studies have demonstrated that HER2 is also present in other cancers, particularly in gastric cancer. [52][53][54][55] Trastuzumab is a critical drug for the treatment of HER2-positive breast cancer that also has been shown to be useful for the treatment of HER2-positive gastric cancer 56 ; it is approved by the European Union, the United States, and China for the treatment of gastric cancer. Currently, there is no report comparing the exhaled metabolomics of these two types of cancer.…”

Impact of HER2 status in resected gastric or gastroesophageal junction adenocarcinoma in a Western population

“…Moreover, the TOXAG study showed that adding trastuzumab to adjuvant radio chemotherapy is tolerable in terms of toxicity, though we currently lack data on its effectiveness [23].…”

A Phase Ii Study Of The Combination Of Oxaliplatin, Capecitabine, And Trastuzumab And Chemo-radiotherapy In The Adjuvant Setting In Operated Patients With Her2+ Gastric Or Gastroesophageal Junction Cancer (Toxag Study), A Turkish Oncology Group Study

“…By pre-de ning an α = 0.10 and β = 0.64, xed comparisons would be carried out by Fisher's Exact test. If the prede ned α value is signi cantly better than the tolerability percentage of 64.0% observed in INT0116, we would continue to recruit more patients up to 40, which was ultimately the responsibility of the Independent Data and Safety Monitoring Committee, which was presented previously [13].…”