Yoshihiko Segawa

Risk factors of chemotherapy‐induced nausea and vomiting: Index for personalized antiemetic prophylaxis

Chemotherapy‐induced nausea and vomiting (CINV) is one of the most problematic adverse events that affects the well‐being of cancer patients. Risk factors for CINV and its elimination are necessary to increase the indications for and effectiveness of chemotherapy. We enrolled 1549 chemotherapy‐naïve patients in two phase II trials and one phase III trial of palonosetron between 2005 and 2007. Treatment failure (any emetic episodes or any administration of rescue medication) and/or nausea, and their associations with patient factors were evaluated in acute and in delayed phases using univariate and multivariate analyses. Female gender (odds ratio, 95% confidence interval: 2.96, 2.09–4.20), age <55 years (2.56, 1.94–3.37), non‐habitual alcohol intake (1.90, 1.43–2.51) and non‐smoker (1.40, 1.04–1.90) were associated with treatment failure in the acute phase. In contrast, only female gender (1.88, 1.34–2.64) was associated with treatment failure in the delayed phase. The number of risk factors was significantly associated with CINV in both acute and delayed phases. Patient risk factors were significantly associated with CINV. Depending on the relationship between CINV‐related risk factors and a tailored antiemetic treatment, high‐risk patients defined by the listed risk factors may be candidates for future clinical trials.

Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials

Introduction: Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first‐line cetuximab chemotherapy. Patients and Methods: The associations of tumor location with overall survival and progression‐free survival were evaluated in mCRC patients with KRAS exon 2 wild‐type tumors who were enrolled onto 2 clinical trials: JACCRO CC‐05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC‐06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right‐sided or left‐sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed. Results: A total of 110 patients were assessable for tumor location; 90 had left‐sided tumors. Left‐sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P < .0001) and progression‐free survival (11.1 vs. 5.6 months, hazard ratio = 0.47, P = .0041) than right‐sided tumors; similar results were obtained in multivariate analysis. A subanalysis showed that the association was evident in the FOLFOX group and that tumor location was an independent prognostic factor irrespective of BRAF status in RAS wild‐type patients. Conclusion: Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first‐line cetuximab combined with oxaliplatin‐based chemotherapy. &NA; Primary tumor location is a prognostic factor in metastatic colorectal cancer (mCRC). We assessed the prognostic impact of tumor location on survival and the association between BRAF mutation and tumor sidedness in mCRC patients treated with cetuximab. Tumor location is a prognostic marker for first‐line cetuximab plus oxaliplatin‐based chemotherapy, irrespective of BRAF status.

A phase II study of cisplatin plus S-1 with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer: The Okayama Lung Cancer Study Group Trial 0501

BACKGROUND Although cisplatin-based chemotherapy combined with thoracic irradiation (TRT) is a standard treatment for unresectable, locally advanced non-small cell lung cancer (NSCLC), this treatment outcome has remained unsatisfactory. We had previously conducted a phase I trial of cisplatin plus S-1, an oral 5-fluorouracil derivative, and TRT, which were safe and effective. METHODS In this phase II trial, 48 patients with stage III NSCLC received cisplatin (40mg/m(2) on days 1, 8, 29 and 36) and S-1 (80mg/m(2) on days 1-14 and 29-42) and TRT (60Gy). The primary endpoint was the response rate. RESULTS A partial response was observed in 37 patients (77%; 95% confidence interval: 63-88%). At a median follow up of 54 months, the median progression-free survival and median survival time were 9.3 and 31.3 months, respectively. No difference in efficacy was observed when the patients were stratified by histology. Toxicities were generally mild except for grade 3 or worse febrile neutropenia and pneumonitis of 8% and 4%, respectively. No patient developed severe esophagitis. At the time of this analysis, 35 (73%) of the 48 patients recurred; 15 (31%) showed distant metastasis, 17 (35%) had loco-regional disease, and 2 (4%) showed both loco-regional disease and distant metastasis. CONCLUSIONS This chemoradiotherapy regimen yielded a relatively favorable efficacy with mild toxicities in patients with locally advanced NSCLC.

Combined assessment of EGFR-related molecules to predict outcome of 1st-line cetuximab-containing chemotherapy for metastatic colorectal cancer.

ABSTRACT Several studies have reported that epidermal growth factor receptor (EGFR)-related molecules may serve as predictors of cetuximab treatment for metastatic colorectal cancer (mCRC), such as EGFR gene copy number (GCN), expression of 2 ligands of EGFR, amphiregulin (AREG) and epiregulin (EREG), and EGFR CA simple sequence repeat 1 (CA-SSR1) polymorphism; however, these biomarkers still remain not useful in clinical practice since they have been evaluated using cohorts with patients treated in various settings of chemotherapy. We therefore analyzed associations of mRNA expression of AREG and EREG, EGFR GCN, and CA-SSR1 polymorphism [short (S;≤ 19) / long (L; ≥ 20)] with clinical outcomes in 77 Japanese patients with KRAS exon 2 wild-type mCRC enrolled in phase II trials of FOLFOX (n = 28/57, UMIN000004197) or SOX (n = 49/67, UMIN000007022) plus cetuximab as first-line therapy. High AREG expression correlated with significantly better progression-free survival (median 11.6 vs. 66 months, HR 0.52, P = 0.037); moreover, it remained statistically significant in multivariate analysis (HR: 0.48, P = 0.027). S/S genotype of CA-SSR1 predicted severe skin toxicity (P = 0.040). Patients with both AREG-low and EGFR low-GCN had significantly shorter overall survival than the others (median 22.2 vs. 42.8 months, HR 2.34, P = 0.042). The multivariate analysis showed that molecular status with both AREG-low and EGFR low-GCN was a predictor of worse survival (P = 0.006). In conclusion, AREG mRNA expression and EGFR CA-SSR1 polymorphism predict survival and skin toxicity, respectively, of initial chemotherapy with cetuximab. Our results also suggest potential prognostic value of the combined assessment of AREG and EGFR GCN for first-line cetuximab treatment.

Long-term combination chemotherapy using eribulin and trastuzumab for three patients with human epidermal growth factor receptor 2-positive metastatic breast cancer

The combination chemotherapy regimen of eribulin (ERI) and trastuzumab (TRA)—the ERI-TRA regimen—has been shown to be highly tolerable for patients with recurrent or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, no sufficient clinical evidence is available for the long-term safety profile of the regimen. We report on three patients in the Phase I combination study of the regimen, for whom the regimen could be conducted over the long term. Patient #1 was a 68-year-old woman and underwent the regimen until cycle 23. Patient #2 was a 61-year-old woman and underwent the regimen until cycle 27. Patient #3 was a 59-year-old woman and underwent the regimen until cycle 22. All these patients had undergone TRA-based combination therapy before the onset of the regimen. Any new categories of adverse events did not occur in association with the long-term combination chemotherapy. Neutropenia experienced by these patients was reversible and easily manageable by dose adjustment (interruption/delay and reduction). Neither increase in the risk of cardiomyopathy nor the worsening of peripheral neuropathy greater than grade 1 was found. The present regimen was suggested to be a novel chemotherapeutic option for patients with HER2-positive recurrent or metastatic breast cancer. The fact that the long-term ERI-TRA regimen was successfully conducted for these patients can be supplementary clinical information that is beneficial for clinical oncologists.