Clinical Significance of Increased Skeletal Muscle Mass During Nab-Paclitaxel Plus Gemcitabine Treatment in Patients With Advanced Pancreatic Cancer.

OBJECTIVES: The clinical significance of increased skeletal muscle mass during nab-paclitaxel plus gemcitabine (AG) treatment in patients with advanced pancreatic cancer (APC) remains unknown. Therefore, we retrospectively investigated the characteristics of patients after AG treatment to evaluate the clinical significance of increased skeletal muscle mass during treatment. METHODS: From January 2015 to August 2021, 67 patients with APC received AG as first-line chemotherapy at Higashiosaka City Medical Center. Of these patients, 39 received second-line (2L) chemotherapy after AG therapy, and 28 received best supportive care. Patients' characteristics at the end of AG treatment were compared retrospectively between these 2 groups, and the relevant factors at the end of first-line treatment for 2L chemotherapy induction were analyzed. RESULTS: A performance status of 0 to 1 and increased skeletal muscle mass during AG therapy were independently associated with 2L chemotherapy induction in multivariate analysis. A high relative dose intensity (≥50%) in the first 8 weeks of AG treatment was more frequently found in patients with increased skeletal muscle mass during treatment ( P = 0.037). CONCLUSIONS: Increased skeletal muscle mass during AG treatment might contribute to the higher prevalence of 2L chemotherapy induction in patients with APC.

Do antihypertensive drugs really have antitumor effects? Baseline differences in hypertensive and non-hypertensive patients with advanced pancreatic cancer.

Although the antitumor effects of antihypertensive drugs for patients with advanced pancreatic cancer (APC) have been investigated, their efficacy remains unclear. Previous studies suggest that hypertensive (HT) patients with APC are significantly older than non-HT patients with APC, and that other major baseline differences in patient characteristics which may affect prognosis exist between HT and non-HT patients. It is also possible that antihypertensive drugs lack antitumor activity. Therefore, we herein retrospectively investigated the baseline differences between HT and non-HT patients with APC. From January 2015 to April 2020, 56 patients with APC received nab-paclitaxel plus gemcitabine as first-line chemotherapy at Higashiosaka City Medical Center (Higashiosaka, Japan). Of these 56 patients, 30 were diagnosed with hypertension (HT group); the remaining 26 did not have hypertension (non-HT group). Differences between the two groups were compared and prognostic factors were evaluated. Patients in the HT group had significantly less sarcopenia, a significantly larger body mass index, were significantly older, and significantly more likely to have a regular doctor and primary site in the body and tail of the pancreas than those in the non-HT group. Although no significant difference was found in the treatment response, patients in the HT group were significantly more likely to move to second-line chemotherapy than those in the non-HT group. Survival curves showed that median overall survival (OS) in the HT group was significantly longer (10.5 months) than in the non-HT group (6.8 months, P = .04). Multivariate analysis did not identify the use of antihypertensive drugs as an independent prognostic factor of OS. We identified key baseline differences in the characteristics of APC patients with and without HT, suggesting that major selection bias could occur when investigating the efficacy of antihypertensive drugs in all populations. Therefore, it is possible that antihypertensive drugs lack antitumor activity. To determine the true efficacy of antihypertensive drugs for APC, HT, and non-HT patients in another population should be investigated, or a prospective, randomized, controlled trial conducted that is stratified by HT or non-HT status.

Baseline Factors Predictive of the Receipt of Second-Line Chemotherapy After Nab-Paclitaxel Plus Gemcitabine for Patients With Advanced Pancreatic Cancer.

OBJECTIVE: Second-line (2L) chemotherapy is important for improved survival in patients with advanced pancreatic cancer (APC). However, approximately half of patients with APC do not receive 2L chemotherapy because of disease progression or adverse events. Baseline factors predictive of the receipt of 2L chemotherapy remain unknown. Therefore, we investigated predictive factors for the receipt of 2L chemotherapy in patients with APC. METHODS: Between January 2015 and March 2020, 53 patients with APC received nab-paclitaxel plus gemcitabine (AG) as first-line chemotherapy at our institute. Of these 53 patients, 29 patients received 2L chemotherapy, and 23 patients received best supportive care. Patients' characteristics were compared retrospectively, and predictive factors for the receipt of 2L chemotherapy were evaluated. RESULTS: Sarcopenia and hypoalbuminemia at baseline were independent negative predictive factors for the receipt of 2L chemotherapy in multivariate analysis. Although the presence of sarcopenia did not affect the relative dose intensity through 8 weeks of AG therapy, patients with hypoalbuminemia had a significantly lower relative dose intensity. CONCLUSIONS: Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.

Predictive implications of decreased CA19-9 at 8 weeks during nab-paclitaxel plus gemcitabine for the induction of second-line chemotherapy for patients with advanced pancreatic cancer.

BACKGROUND: Second-line (2L) chemotherapy after nab-paclitaxel plus gemcitabine (AG) is important for improving the survival of patients with advanced pancreatic cancer (APC). However, many patients fail to receive 2L chemotherapy because of rapid disease progression. Therefore, early recognition of any ineffectiveness during AG might lead to an increased induction rate of 2L chemotherapy. AIM: We investigated the significance of treatment response at 8 weeks as a predictive factor for the induction of 2L chemotherapy after AG. METHODS AND RESULTS: From January 2015 to January 2019, 41 patients with APC underwent AG as first-line chemotherapy at our institute. Thirty-three patients were evaluated at 8 weeks. Sixteen patients (48%) underwent 2L chemotherapy and 17 (52%) underwent no 2L chemotherapy. Clinical features and treatment response at 8 weeks were, retrospectively, compared among patients. Predictive factors for the induction of 2L chemotherapy were analyzed. Patients with an objective response by 8 weeks received 2L chemotherapy more frequently (P = .026). Decreased CA19-9 (<50%) at 8 weeks was identified as an independent negative predictive factor for the induction of 2L chemotherapy. CONCLUSIONS: Decreased CA19-9 (<50%) at 8 weeks may indicate the ineffectiveness of AG and signify that a move to 2L chemotherapy may be required without delay.

Efficacy of S-1 in second-line chemotherapy after nab-paclitaxel plus gemcitabine for patients with advanced pancreatic cancer.

BACKGROUND: Second-line (2 L) chemotherapy is important for improved survival. However, the efficacy of S-1 after nab-paclitaxel plus gemcitabine (AG) for advanced pancreatic cancer (APC) remains unclear. AIM: We retrospectively investigated the clinical impact of S-1 after AG. METHODS AND RESULTS: From January 2015 to July 2018, 37 patients with APC underwent AG as first-line chemotherapy at our institute. Of these patients, 14 (38%) underwent S-1 as 2 L chemotherapy after AG (S-1 group), five (14%) received another agent after AG, and 18 (49%) underwent no 2 L chemotherapy (best supportive care [BSC] group). The clinical features were retrospectively compared between the S-1 and BSC groups. Prognostic factors for residual survival (RS) were analyzed using a Cox proportional hazards model. The induction rate of 2 L chemotherapy was 51%, and most patients received S-1 monotherapy (74%). The disease control rate and progression-free survival duration were 57.1% and 2.8 months, respectively. The median RS duration in the S-1 and BSC groups was 5.2 and 2.4 months, respectively; this difference was statistically significant (hazard ratio, 0.33; P = .005). The median overall survival duration in the S-1 and BSC groups was 12.3 and 5.0 months, respectively; this difference was also statistically significant (hazard ratio, 0.26; P = .001). The efficacy of S-1 in 2L chemotherapy for RS was identified in the multivariate analysis, as was age (<65 vs ≥65 y) and the presence of liver metastasis. CONCLUSION: The antitumor activity of S-1 was retained after AG, and the induction of S-1 after AG might improve the prognosis of patients with APC.

Phase II study of bi-weekly irinotecan for patients with previously treated HER2-negative metastatic breast cancer: KMBOG0610B.

BACKGROUND: A trial was conducted to evaluate the feasibility, efficacy, and safety of biweekly administration of irinotecan, a novel topoisomerase I inhibitor, for patients with metastatic breast cancer (MBC) previously treated with either anthracycline-based or taxane-based chemotherapy. METHODS: Eligible patients were HER2-negative, had a performance status of 0 to 2, and had been treated previously with either anthracyclines or taxanes for MBC. Patients received irinotecan intravenously at 150 mg/m(2) on days 1 and 15 every 4 weeks. The primary end-point was feasibility, and the treatment was considered feasible if a patient was able to receive three administrations of irinotecan within the first 8 weeks, as pre-specified in the protocol. RESULTS: Eighteen patients (median age 60 years) were enrolled. Fifteen patients received irinotecan more than 3 times within the first 8 weeks, with resulting feasibility of 83.3%. The median number of treatment cycles was 2 (range 1-16) during this period, and the relative dose intensity was 91.2%. Partial response was observed for one patient, so overall response rate was 5.6%. Nine patients (50.0%) had stable disease, and overall disease control was 50.0%. Median progression-free survival and overall survival periods were 3.2 and 9.6 months, respectively. The only grade 3/4 hematological toxicity was neutropenia (22.2%). Grade 3/4 non-hematological toxicities were anorexia (11.2%), diarrhea (11.2%), and fatigue (5.6%). No treatment-related death occurred. CONCLUSIONS: This study demonstrated that biweekly administration of 150 mg/m(2) irinotecan was feasible for patients with MBC treated previously with anthracyclines or taxanes.

A phase II study of irinotecan in combination with doxifluridine, an intermediate form of capecitabine, in patients with metastatic colorectal cancer.

The purpose of this study was to examine the efficacy of a combination treatment of sequential irinotecan and doxifluridine, an intermediate of capecitabine, evaluated by the response rate and safety in patients with metastatic colorectal cancer. In all, 60 metastatic colorectal cancer patients with measurable disease were enrolled. The schedule of the treatment consisted of a 90 min intravenous (IV) infusion of irinotecan 150 mg/m2 for on days 1 and 15, and 600-1,000 mg/body of oral doxifluridine on days 3-14 and 17-28. Cycles were repeated every 35 days. A median of three cycles of the combination therapy (range 1-14 cycles) was administered. A total of 57 patients (95%) completed at least two cycles of the therapy without any dose reductions. There was one complete response and 23 partial responses with an overall response rate of 40% [95% confidence interval (CI): 28-53%]. A total of 19 patients had stable disease, 43(72%) achieved disease control. The median time to progression was 5.9 months and the median overall survival was 20.5 months. Ten (17%) and 17 (28%) patients developed Grade 3-4 leukopenia and neutropenia, respectively. Grade 3-4 fatigue was observed in 7(12%) patients, nausea in five (8%), vomiting in four (7%), and diarrhea,in three (5%) patients. No treatment-related deaths were noted during the study. From these results, the combination of sequential irinotecan and doxifluridine is considered to be an effective, easy-to-administer regimen with acceptable tolerability.

A case of invasive lobular carcinoma of the breast first manifesting with duodenal obstruction.

Lobular carcinoma of the breast presents with various clinical manifestations. Lobular carcinoma comprises about one fifth of cases of ductal carcinoma. Intestinal metastasis is dominant in cases of lobular carcinoma. Without a prior diagnosis of lobular carcinoma of the breast, the diagnosis of intestinal metastasis from breast cancer is difficult. A 52-year-old women underwent duodenogastrectomy for duodenal cancer. About 18 months later, she underwent mastectomy for lobular carcinoma of the breast. The duodenal cancer consisted mainly of malignant cells invading the submucosa that were identical to those in the breast. Immunohistochemical assays for estrogen receptor also confirmed breast cancer metastasis. Duodenal obstruction was the first sign of isolated metastatic lobular carcinoma of the breast in this case. The characteristic metastatic pattern of lobular carcinoma, which differs from that of ductal carcinoma, should be kept in mind to ensue proper diagnosis. Preceding breast surgery for lobular carcinoma should prompt investigation based on the typical metastatic pattern.

Application of RT-PCR to clinical diagnosis of micrometastasis of colorectal cancer: A translational research study.

We previously reported in a retrospective study that CEA-based RT-PCR was useful for predicting the prognosis of patients with node-negative colorectal cancer. RT-PCR is well established for laboratory use, but many issues remain to be resolved prior to its clinical application. In addition to the false positive rate of RT-PCR, we addressed several issues, including the timing of lymph node sampling, stability of RNA after surgery, and reproducibility of results. After appropriate modification, including development of a tissue sampling kit, a multi-institutional clinical study was commenced prospectively from November 2001, and 100 patients were enrolled for examination of micrometastasis. RNA was stable in lymph nodes for up to 3 h after surgical resection. This range of sampling time was acceptable to the surgeons. RNA was well preserved in RNA later at -20 degrees C for 3 weeks. Dilutions of MKN45 and LoVo cells served as positive controls for conventional PCR since these controls were found to be highly stable and ensured reproducibility. Moreover, simultaneous use of quantitative PCR (Light Cycler) ensured double confirmation of the results. Our clinical study showed that the quality of RNA was excellent or good in most samples (98 of 100; 98%). Twenty-four of 98 (24.5%) cases were judged to be micrometastasis-positive. In conclusion, the current translational research study established a clinically feasible RT-PCR system for micrometastasis. Our system could potentially be useful as a clinical tool.