Tegafur and 5-fluorouracil levels in tears and changes in tear volume in long-term users of the oral anticancer drug S-1.

Eye problems are an adverse reaction sometimes found in chemotherapy. Although not life-threatening, they can reduce patients' quality of life. The highest incidence of eye problems is reported for the combination anticancer drug S-1 (tegafur-gimeracil-oteracil), and methods to prevent or treat the eye problems caused by this drug are presently lacking. To determine early detection methods and treatment for adverse ocular reactions, we measured changes in tear volume and levels of tegafur (FT) and 5-fluorouracil (5-FU), an active metabolite of FT, in the tears of patients with long-term use of S-1. A total of 11 patients receiving S-1 monotherapy as adjuvant chemotherapy after gastric cancer surgery were included. Tear volume and FT and 5-FU levels in tears were measured by liquid chromatography with tandem mass spectrometry during a maximum of 8 treatment cycles (48 weeks). For analysis, patients were divided into two groups: "watering eyes" (n=6, complaints of watering eyes at least once during the treatment period) and "no watering eyes" (n=5, no complaints of watering eyes). Both groups exhibited increased FT and 5-FU levels in tears upon initiation of S-1 treatment, and levels rapidly decreased upon discontinuation. Our findings suggest a relationship between FT level in tears and tear volume in patients with long-term S-1 use. The symptom of watering eyes may thus be linked to FT level in tears.

A single-arm, phase 2 study of steroid-containing mouthwash for the prevention of everolimus-associated stomatitis in multiple tumor types.

BACKGROUND: Everolimus is a mammalian target of rapamycin inhibitor used in the treatment of multiple tumor types, and its most common toxicity, stomatitis, can affect patient quality of life. Recent studies in breast cancer have supported the efficacy of steroid mouthwash for the prevention of everolimus-associated stomatitis. However, a few studies have been reported to date, and none have examined this effect in other tumor types. METHODS: This single-arm phase 2 study was designed to evaluate the efficacy of steroid-containing mouthwash for the prevention of stomatitis in patients with multiple tumor types receiving everolimus. The primary outcome was incidence of grade ≥ 2 stomatitis at 8 weeks of everolimus with steroid-containing mouthwash prophylaxis. We also assessed the stability of steroid-containing mouthwash components. RESULTS: Twenty-nine patients were evaluated, of which 76% had breast cancer and 24% had neuroendocrine tumors originating in the lung, gastrointestinal tract, pancreas, or of unknown primary origin. Grade ≥ 2 stomatitis incidence at 8 weeks was 28.1% (90% CI 16.2-46.1); the higher confidence limit exceeded the prespecified threshold of 30%. No patients developed grade ≥ 3 stomatitis. Most stomatitis occurred behind the oral cavity, with no lesions observed on the lips or floor of the mouth. CONCLUSIONS: Our findings did not support a prophylactic effect of steroid-containing mouthwash on everolimus-associated stomatitis. Given the needs of prevention of everolimus-associated stomatitis in various tumor types, further studies in a larger population using a randomized controlled trial design are, therefore, required to confirm the efficacy of steroid-containing mouthwash.

Changes in tear volume and ocular symptoms of patients receiving oral anticancer drug S-1.

BACKGROUND: Most eye disorders are not fatal but may deteriorate the quality of life of a patient. The eye disorder that is most frequently reported in the cancer chemotherapy is associated with the combination of tegafur/gimeracil/potassium oxonate (S-1). However, preventive methods or treatment methods for the eye disorder have not yet been established. This study aimed to determine changes in tear volume and subjective ocular symptoms during the treatment period in patients receiving S-1 monotherapy for early detection of adverse effects in the eye and establishment of its treatment methods. METHODS: This study included eleven patients receiving S-1 monotherapy as a postoperative adjuvant chemotherapy for gastric cancer. Six subjective ocular symptoms including watering eyes were evaluated and changes in tear volume measured by the Schirmer's test in patients receiving S-1 during the treatment period. In the present study, the patients were divided into "no watering eyes" (patients not experienced watering eyes) group and "watering eyes" (patients experienced watering eyes even once) group. RESULTS: Six out of eleven patients developed watering eyes after receiving S-1 monotherapy. Among these, the earliest onset occurred on the 2nd week after oral administration. Watering eyes and eye discharge were highly related in patients having a trouble in daily life due to the decreased QOL. Changes in tear volume in the "watering eyes" group significantly increased compared to the "no watering eyes" group during the treatment period, especially when the patients had no subjective symptom of the increased tear volume. CONCLUSIONS: It is essential to prevent eye disorders including watering eyes as an adverse effect of S-1 administration. The present study recommends that the tear volume should be periodically measured using Schirmer's test, and the patient should be interviewed regarding the subjective ocular symptoms for the early detection of watering eyes caused by S-1 administration. If the tear volume can not be measured periodically, medical staffs should pay attention to the patient with eye discharge.

[Qualitative Research to Investigate the Needs of Pharmacists and Drug Therapy of Cancer Patients].

We performed a survey of cancer patients' needs for drug treatment and support from pharmacists during treatment and evaluated the support that cancer patients can expect from community pharmacists in the future. The patients consisted of 16 members of the Cancer Patient Association in Aichi prefecture who underwent chemotherapy. The results of a semistructured group interview were qualitatively analyzed using the grounded theory method. Patients undergoing chemotherapy had high hopes for its effectiveness but were worried about side effects and medical costs. To overcome these problems, they hoped for a decrease in the economic burden, compassionate-use system, and development of novel drugs. The patients had anxiety because the side effects of chemotherapy often caused physical and psychological damage. Despite patients' confusion, pharmacists sometimes did not give adequate explanations to them. The patients expected more from pharmacists regarding medication support and hoped for a system allowing continuous side effect monitoring and consultation without hesitation. For patients undergoing cancer chemotherapy who are confused regarding side effects, pharmacists should understand the patient explanatory model and become more involved with patients as partners in treatment.

Serum concentration of fentanyl during conversion from intravenous to transdermal administration to patients with chronic cancer pain.

BACKGROUND: To the best of our knowledge, there have been no reports on the pharmacokinetics and pharmacodynamics during the conversion from continuous intravenous infusion (CII) to transdermal fentanyl administration. The primary objective of the present study was to clarify the pharmacokinetic characteristics during this conversion. A secondary objective was to identify an association between serum albumin and the absorption of fentanyl from the transdermal patch. METHODS: A prospective study was conducted from February 2010 to August 2011 that enrolled 19 patients with chronic cancer pain. Patients were classified into 2 study groups according to body mass index and albumin level. All patients received the conversion from CII to transdermal fentanyl using a 2-step taper of CII over 6 hours. Comparisons of efficacy, toxicity, and serum fentanyl concentrations between study groups were analyzed at baseline, 3, 6, 9, 12, 15, 18, and 24 hours after initiation of the conversion. RESULTS: The dose-adjusted serum fentanyl concentrations for all patients were significantly decreased at 15 to 24 hours after conversion compared with baseline, although pain intensity and the number of rescue events remained stable during the conversion. The dose-adjusted serum fentanyl concentrations at 9 to 24 hours were significantly reduced in the low albumin group compared with the normal albumin group (P<0.05). CONCLUSIONS: Our study demonstrated that the dose-adjusted serum fentanyl concentrations remained relatively stable, and pain intensity and the number of rescue events remained stable during conversion. Hypoalbuminemia was strongly associated with poor absorption of transdermally administered fentanyl.

[Antiemetic effect of palonosetron in advanced colorectal cancer patients receiving mFOLFOX6 and FOLFIRI: a retrospective survey].

Controlling chemotherapy-induced nausea and vomiting(CINV)is very important for the continuation of chemotherapy. CINV can significantly affect a patient's quality of life, leading to poor compliance with further chemotherapy treatment. In this retrospective study, we assessed the efficacy of palonosetron versus granisetron for the incidence of CINV induced by mFOLFOX6 and FOLFIRI in patients with advanced colorectal cancer. Eighty-eight patients were included in the efficacy analyses: 39 patients in the palonosetron group and 49 patients in the granisetron group. The incidence of nausea in the granisetron group(Grade 1: 40. 8%, Grade 2: 10. 2% and Grade 3: 4. 1%)was significantly higher than in the palonosetron group (Grade 1: 25. 6% and Grade 2: 7. 7%, p=0. 0422). The incidence of vomiting and appetite loss in the granisetron group was not significantly higher than in the palonosetron group(p=0. 2419, p=0. 2648, respectively). This suggests that palonosetron exerts better efficacy against chemotherapy-induced nausea than granisetron in patients receiving mFOLFOX6 and FOLFIRI. Information on such analyses is useful to promote the effectiveness of cancer chemotherapy.

[Induced nausea and vomiting induced by mFOLFOX6 and FOLFIRI with advanced colorectal cancer: a retrospective survey].

Controlling of chemotherapy-induced nausea and vomiting (CINV) is very important for the continuation of chemotherapy, especially for outpatients. CINV can significantly affect a patient's quality of life, leading to poor compliance with further chemotherapy treatment. In this retrospective study, we investigated the incidence of CINV induced by mFOLFOX6 and FOLFIRI in 59 outpatients (32 males and 27 females) with advanced colorectal cancer to evaluate CINV severity using the Common Terminology Criteria for Adverse Events v.3.0. The incidence of nausea in the female group receiving FOLFIRI (grade 1: 66.7% and grade 2: 20.0%) was significantly higher than that in the male group (grade 1: 23.1% and grade 2: 7.7%, p=0.0066). The incidence of nausea in the younger (<63 years old) group receiving FOLFIRI (grade 1: 57.1% and grade 2: 28.6%) was significantly higher than that in the older (≧63 years old) group (grade 1: 35.7%, p=0.0031). Multivariable logistic regression analysis indicated that patients who were female or younger had a significantly higher incidence of nausea or vomiting than patients who were male or older, respectively, when treated with FOLFIRI. This suggests that gender (female) and age (younger) are factors predicting poor antiemetic control in outpatients receiving FOLFIRI, but not those treated with mFOLFOX6. Information on such predictive factors should be useful to promote the effectiveness of cancer chemotherapy.

[Investigating the incidence of injection-site reactions associated with administration of oxaliplatin into a peripheral vein and management local adverse reactions].

In Aichi Cancer Center Hospital, we investigated the incidence of injection-site reactions associated with the administration of Oxaliplatin into a peripheral vein. We evaluated the frequency and severity of symptoms, and studied ways to manage its adverse reactions from September 2009 through March 2010. Oxaliplatin was injected into a peripheral vein in more than 90% of patients, suggesting that there would be a high risk of injection-site reactions. About 60% of patients had a numeric rating score of 5 or higher in this study, and more than 60% of injection-site reactions were improved by warming the injection site. Our results suggest that warming the injection site is one effective way to manage local adverse reactions when Oxaliplatin is administered into a peripheral vein.

[Incidence of infusion reactions induced by cetuximab chemotherapy].

We retrospectively investigated the incidence of infusion reactions following cetuximab chemotherapy in 93 patients with colorectal cancer. Patients received chemotherapy treatment from September 2008 to February 2010 at Aichi Cancer Center Hospital. The initial cetuximab dose was 400 mg/m(2), followed weekly by an additional 250 mg/m(2), and biweekly by 500 mg/m(2). Infusion reactions were observed in 12 patients (13%), with grade 1 reactions in 6 patients and grade 2 reactions in 6 patients. Eleven of the 12 patients (92%) experienced infusion reactions during the first treatment. Typical grade 1 adverse events were fever and chills, nausea, vomiting and pruritus. Non-steroidal anti-inflammatory drugs were given for fever and chills. Grade 2 adverse events included dyspnea and wheezing, eruption, facial flushing and convulsions. Steroids were given for these symptoms. Infusion reactions were observed in 3 of the 12 patients (25%) <15 min after intravenous injection, 16-60 min after injection in 3 more patients (25%), and 61-120 min after injection in the remaining 6 patients (50%).