Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review.

BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. MATERIAL AND METHODS: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received ≥1 cycle of either S-1 (n = 9), SOx (n = 44) or IRIS (n = 18) for mCRC. Median age was 76 years and most patients had a WHO performance status of 0 (32%) or 1 (56%). All patients were evaluable for response and safety. In the SOx group, 18 (41%) and 20 patients (45%) had partial response (PR) and stable disease (SD), respectively (disease control rate 86%). Median progression-free survival (PFS) was 8.5 months and median overall survival (OS) was 18.5 months. In the S-1 group (median age 82 years), PR was 22%, median PFS 6.4 months and median OS 15.8 months. In the IRIS group, PR was 28%, median PFS 7.8 months and the median OS 16.5 months. In general, therapy was well tolerated; main non-hematological toxicities were fatigue and diarrhea. CONCLUSION: S-1 monotherapy, SOx and IRIS were well tolerated for older patients with mCRC and could become alternative regimens in older mCRC patients. These regimens are now further evaluated in the randomized ongoing NORDIC9 trial.

S-1 (Teysuno) and gemcitabine in Caucasian patients with unresectable pancreatic adenocarcinoma.

PURPOSE: Gemcitabine has been standard of care in advanced pancreatic adenocarcinomas (PC) for almost two decades. Randomized, primarily Japanese, studies have shown promising efficacy when combined with S-1 (GemS-1); however, no data are published in Caucasian patients. We report the first study with a combination of GemS-1 in an unselected cohort of Caucasian PC patients. METHODS: In this observational cohort study, we analyzed efficacy and toxicity prospectively. RESULTS: From July 2012 to July 2014, 64 patients received at least one cycle of GemS-1. 16 patients started therapy with gemcitabine and capecitabine (GemCap) but switched to GemS-1 after median 3 cycles of GemCap due to toxicity (hand-foot syndrome). 48 patients received GemS-1 as initial therapy. For the complete cohort, median age was 68 years (range 44-80); 22 patients (34%) had locally advanced PC; 42 patients (66%) had metastatic disease. Five patients had received prior adjuvant therapy with gemcitabine and 9 pts had received prior first-line therapy. The most common adverse event was fatigue (86%), however, only grade 3 in 3%. Five patients (8%) developed febrile neutropenia. Median PFS was 8.1 (95% CI 6.9-9.0) months and median OS was 11.7 (95% CI 10.7-13.1) months in the whole GemS-1 population. In the 48 patients starting with GemS-1, median PFS was 7.7 (95% CI 6.7-8.9) months and median OS was 11.5 (95% CI 9.7-12.3) months. CONCLUSIONS: The combination of gemcitabine and S-1 is safe and associated with promising efficacy in a Caucasian population; however, this needs to be confirmed in prospective clinical trials.

Multi-institutional quantitative evaluation and clinical validation of Smart Probabilistic Image Contouring Engine (SPICE) autosegmentation of target structures and normal tissues on computer tomography images in the head and neck, thorax, liver, and male pelvis areas.

PURPOSE: Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE). METHODS AND MATERIALS: CT images of 125 treated patients (32 head and neck [HN], 40 thorax, 23 liver, and 30 prostate) in 7 independent institutions were autosegmented using SPICE and computational times were recorded. The number of structures autocontoured were 25 for the HN, 7 for the thorax, 3 for the liver, and 6 for the male pelvis regions. Using the clinical contours as reference, autocontours of 22 selected structures were quantitatively evaluated using Dice Similarity Coefficient (DSC) and Mean Slice-wise Hausdorff Distance (MSHD). All 40 autocontours were evaluated by a radiation oncologist from the institution that treated the patients. RESULTS: The mean computational times to autosegment all the structures using SPICE were 3.1 to 11.1 minutes per patient. For the HN region, the mean DSC was >0.70 for all evaluated structures, and the MSHD ranged from 3.2 to 10.0 mm. For the thorax region, the mean DSC was 0.95 for the lungs and 0.90 for the heart, and the MSHD ranged from 2.8 to 12.8 mm. For the liver region, the mean DSC was >0.92 for all structures, and the MSHD ranged from 5.2 to 15.9 mm. For the male pelvis region, the mean DSC was >0.76 for all structures, and the MSHD ranged from 4.8 to 10.5 mm. Out of the 40 autocontoured structures reviews by experts, 25 were scored useful as autocontoured or with minor edits for at least 90% of the patients and 33 were scored useful autocontoured or with minor edits for at least 80% of the patients. CONCLUSIONS: Compared with manual contouring, autosegmentation using SPICE for the HN, thorax, liver, and male pelvis regions is efficient and shows significant promise for clinical utility.

[Treatment of unresectable locally advanced pancreatic cancer with combined radiotherapy and chemotherapy]. / Kombineret strålebehandling og kemoterapi til patienter med ikkeresektabel lokalavanceret pancreascancer.

INTRODUCTION: Only 10-20% of patients with pancreatic cancer are offered operation with curative intent. If this is not possible, treatment with pre-operative radiotherapy in combination with chemotherapy offers the opportunity to reduce tumor size in patients with locally advanced disease, and possibly resection with curative intent afterwards. This treatment has been offered for the last three years at the Department of Oncology, Odense University Hospital. In the following we present our results. MATERIALS AND METHODS: A total of 26 patients with locally advanced unresectable pancreatic cancer were offered a combination of radiotherapy and chemotherapy. 4-6 weeks after treatment the patients were evaluated for resection. RESULTS: Of the 26 patients 24 completed planned treatment. Eight patients were subsequently assessed resectable. One patient refused surgery; the other 7 patients had a R0-resection. Median survival for the whole group is 12 months. Six of the patients who went through surgery are without signs of recurrent disease after median 16 months, one patient died with recurrent disease after 37 months. CONCLUSION: These results are similar to results from other countries. Therefore patients with locally advanced unresectable pancreatic cancer should be offered radiotherapy in combination with chemotherapy. Evaluation for surgery should be carried out 4-6 weeks after end of treatment. This strategy offers the opportunity for R0-recection and consequently cure.

[New treatment strategies for patients with primary non-resectable rectal cancer]. / Ny behandlingsstrategi for patienter med primaer, ikkeresektabel rectumcancer.

INTRODUCTION: Patients with locally advanced rectal cancer (LARC) have a poor prognosis. Preoperative radiotherapy may shrink the tumour and make subsequent resection possible. The use of modern principles of preoperative radiotherapy in combination with chemotherapy and an active surgical attitude increases the chance for radical surgery and cure. MATERIALS AND METHODS: A single-institution, prospective evaluation of a new treatment strategy in patients with LARC was done. RESULTS: From 1998 to 2000, 20 patients with LARC were treated with high-dose radiochemotherapy (60 Gy and chemotherapy, UFT/leucovorin), and resectability was evaluated four to six weeks after termination of radiochemotherapy. Sixty percent of the patients subsequently had microscopic radical surgery. CONCLUSION: Patients with LARC should preferably be treated with high-dose preoperative radiotherapy in combination with chemotherapy. Evaluation of resectability should be performed at least four weeks after termination of radiotherapy. This strategy, in combination with modern surgical techniques, increases the probability of success of radical surgery and cure.

Short-time infusion of oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) in patients with advanced colorectal cancer.

Neuropathy exacerbated by exposure to cold is a dose-limiting toxicity of oxaliplatin. The incidence of this side effect is claimed to dependent on infusion rate and therefore a 2-h infusion is often recommended. For practical reasons and for the convenience of the patient, we used XELOX (Xeloda 2000 mg/m2 orally on days 1-14 and oxaliplatin 130 mg/m2 as a 30-min infusion on day 1) in patients with advanced colorectal cancer resistant to irinotecan and 5-fluorouracil. Thirty-four consecutive patients received a median of 5 courses of XELOX. Nine patients obtained partial response (PR) (response rate (RR) 26%), 11 patients no change (NC), 7 patients disease progression (PD) and 7 patients were not evaluable. Median time to progression was 4.7 (2.6-7.6) months and median survival was 7.4 (6.0-11.3) months. Sixteen patients had neuropathy grade 1, four patients grade 2 and two patients grade 3. Short-time infusion of oxaliplatin and capecitabine is an active and convenient second-line regimen with a safety profile similar to that of other oxaliplatin schedules.