Breakthrough pain management using fentanyl buccal tablet (FBT) in combination with around-the-clock (ATC) opioids based on the efficacy and safety of FBT, and its relationship with ATC opioids: results from an open-label, multi-center study in Japanese cancer patients with detailed evaluation.

OBJECTIVE: Rapid analgesic onset opioids, particularly fentanyl buccal tablet, is preferable for managing breakthrough pain. The efficacy and safety of fentanyl buccal tablet and its association with around-the-clock opioids needs to be explored with an option of dose adjustments, more closely reflecting administration in clinical practice. The aim of the study was to assess the safety and efficacy of fentanyl buccal tablet in breakthrough pain management in combination with around-the-clock opioids with the dose adjustment option, and explore the dose adjustment's influence on breakthrough pain management using detailed evaluation. METHODS: The 12-week open-label, multi-center study was conducted throughout Japan. Cancer patients aged 20 years or older, experiencing persistent pain controlled with around-the-clock opioids and breakthrough pain with supplemental medications were enrolled. Fentanyl buccal tablet and around-the-clock opioid doses could be adjusted under protocol-specified conditions. Efficacy variables were assessed at each fentanyl buccal tablet administration. Safety was assessed mainly by adverse events. RESULTS: All efficacy variables showed sustained analgesic effect. Nearly half the patients stayed on the same dose; most fentanyl buccal tablet administrations did not require additional supplemental medications. Dose increase of fentanyl buccal tablet and around-the-clock opioids seemed to improve breakthrough pain intensity and frequency, respectively. Fentanyl buccal tablet and around-the-clock opioid doses were not strongly associated. Treatment-related adverse events were all common with opioid treatment and did not increase over time. CONCLUSIONS: Fentanyl buccal tablet can stably and safely manage breakthrough pain in cancer patients with independent dose adjustment based on detailed evaluation of each patient's condition. Breakthrough pain management using fentanyl buccal tablet with around-the-clock opioids at optimal doses may be an important factor in palliative care for cancer patients with breakthrough pain.

A randomized, double-blind, placebo-controlled study of fentanyl buccal tablets for breakthrough pain: efficacy and safety in Japanese cancer patients.

CONTEXT: Rapid-onset opioids for treating breakthrough pain (BTP) in patients with cancer are needed in the Japanese care setting. OBJECTIVES: To examine the efficacy and safety of fentanyl buccal tablets (FBTs) for treating BTP in Japanese cancer patients. METHODS: This was a randomized, double-blinded, placebo-controlled study. In subjects receiving around-the-clock (ATC) opioids at doses of 30 mg or more to less than 60 mg or 60-1000 mg of oral morphine equivalents (low and high ATC groups), dose titration was started from 50 to 100 µg FBT, respectively. Subjects whose effective dose was identified were randomly allocated to a prearranged administration order of nine tablets (six FBTs and three placebos), one tablet each for nine episodes of BTP (double blinded). Efficacy and safety of FBT were assessed for patients overall, and also for the low and high ATC groups. RESULTS: A significant difference was observed between FBT and placebo for the primary endpoint of pain intensity difference at 30 minutes. The analgesic onset of FBT was observed from 15 minutes in several secondary variables (e.g., pain relief). Adverse events were somnolence and other events associated with opioids were mostly mild or moderate. Of the low and high ATC group subjects, an effective FBT dose was identified in 72.2% and 73.1%, respectively. CONCLUSION: The safety of FBT and its analgesic effect on BTP were confirmed in Japanese cancer patients receiving opioids. Our findings suggest that analgesic onset may occur from 15 minutes after FBT, and that FBT can be administered to patients with low doses of ATC opioids.

[Successful chemotherapy with a docetaxel regimen for primary signet-ring cell carcinoma of the urinary bladder-a case report].

Primary signet-ring cell carcinoma of the bladder is rare and has a poor prognosis. In addition, there are few successful chemotherapies for it. We report a case of chemotherapy with a docetaxel regimen which was efficacious in a 64-year-old Japanese man suffering from the disease. The onset of bilateral hydronephrosis led to the detection of his bladder tumor, and its pathological diagnosis was signet-ring cell carcinoma(immunohistochemistry showed cytokeratin 7+/20±). He was treated with chemotherapy rather than with surgery because the tumor invaded the abdominal wall and groin. To treat his disease, we performed 2 courses of a chemotherapy regimen comprised of S-1 and cisplatin, but it was not efficacious. We chose docetaxel as a second-line chemotherapy regimen,(60mg/m2, tri-weekly), and a clinical examination including contrast-enhanced CT showed that his disease had successfully responded to the chemotherapy.

Detection of asymptomatic cardiac metastasis and successful salvage chemotherapy comprising a prednisone, Etoposide, procarbazine, and cyclophosphamide regimen in an elderly Japanese patient suffering from a delayed recurrence of diffuse large B-cell lymphoma.

We report a case of facial diffuse large B-cell lymphoma (DLBCL) associated with recurrent metastasis in the heart and other sites in a 76-year-old Japanese woman. Initially, she developed DLBCL in her left upper eyelid that spread into the left orbit (Ann Arbor classification stage I). The lesion went into clinical regression after 4 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy followed by radiotherapy. More than 3 years later, the lymphoma recurred in her facial skin, together with metastases in the mediastinal lymph nodes and the heart; the tumor in the heart was successfully detected by PET/CT and cardiac MRI. To treat the recurrent lesions, we performed a salvage chemotherapy regimen comprising prednisone, etoposide, procarbazine, and cyclophosphamide, which successfully induced tumor regression.

[A case of mucinous cystadenocarcinoma of the appendix with abdominal wall abscess successfully treated by percutaneous drainage and systemic chemotherapy-a case report].

A 76-year-old woman was diagnosed of mucinous cystadenocarcinoma of the appendix. Since there was wide direct invasion into the right psoas muscle, she was judged as inoperable although she had no bowel obstruction. She was received FOLFIRI and bevacizumab treatment. After the first cycle, the tumor progressed rapidly and formed the abdominal wall abscess at the right groin. Since she had a fever and pain at the right groin and the abscess reached the hypodermic, we put a drainage tube into the abscess. The tube was placed, which made her symptoms improved markedly. We have been continuing with FOLFIRI treatment and drainage for 10 months without progressive disease. We report a rare case of the conservative therapy of mucinous cystadenocarcinoma of appendix with abdominal wall abscess.

[A retrospective study of oral adverse events with colorectal cancer chemotherapy using bevacizumab].

PURPOSE: We encountered serious oral mucositis in some patients undergoing colorectal chemotherapy with bevacizumab. We retrospectively investigated the role bevacizumab plays in the occurrence of oral mucositis. SUBJECTS AND METHODS: Between January 2008 and December 2009, we encountered 11 patients for whom chemotherapy with bevacizumab had resulted in oral mucositis. The patients included 5 men and 6 women, with a mean age of 67. 9 years(range, 62-76 years). Among the patients, 5 had grade 1 oral mucositis, 3 had grade 2, and 3 had grade 3. We analyzed the risk factors, grades, symptoms, and treatments of oral mucositis in these patients. RESULTS: In 6 patients, bevacizumab was administered in combination with mFOLFOX6, and in 5 patients, bevacizumab was administered in combination with FOLFIRI. Seven patients had undergone prior treatment without the occurrence of serious oral mucositis. With respect to oral health, 8 patients had periodontal disease, 7 had dental caries, 3 wore dentures, 3 exhibited poor oral self-care, and 2 had diabetes; in addition, 2 patients were smokers. Symptoms of oral mucositis included mucosal reddening in 11 patients, oral mucosal erosion or ulcer in 7, fungus infection in 6, aphtha in 7, pseudomembrane formation in 3, and poor oral intake in 2. All the patients had oral mucositis at the occlusal line of the buccal mucosa. The treatment for oral mucositis included polaprezinc. CONCLUSION: Because many factors influence the development of oral mucositis, determining the specific cause of oral mucositis is difficult. Bevacizumabmay possibly decrease the VEGF levels in saliva and delay wound healing in oral mucositis. Therefore, oral mucositis may be caused not only by diabetes and poor oral self-care but by bevacizumab.

[A case of triple malignant tumors consisting of esophagus, stomach and malignant lymphoma with a histopathological feature of collision between gastric cancer and malignant lymphoma--a case report].

We report a rare case of a collision between a gastric cancer and a malignant lymphoma with a wide systemic metastasis, combined with esophagus cancer, stomach cancer and malignant lymphoma. A 73-year-old man complained of gross hematuria and swelling of the right testis. Magnetic resonance imaging (MRI) revealed that both testes were swollen with unequal contrast and there were numerous tumors in the retroperitoneal space and pelvis. He was diagnosed with malignant diffuse large B cell lymphoma by immunostaining from the extirpated right testis. He received six cycles of R-CHOP therapy. After the second cycle, partial remission was recognized, but the tumors spread again by the fourth cycle. Thereafter, we performed MTX-HOPE therapy as a salvage therapy for four cycles. During this chemotherapy, he felt epigastralgia; esophagus cancer (squamous cell carcinoma) and stomach cancer (highly-differentiated adenocarcinoma) were found by upper endoscopy. However, the gastrointestinal cancer was inoperable, since the malignant lymphoma was progressive. His general status had been exacerbated, and he died about one year after he was diagnosed with malignant lymphoma. Pathological examination revealed that the adenocarcinoma had partly collided with the malignant lymphoma.

[A case of multiple metachronous metastases of colon cancer to the small intestine preoperatively diagnosed by double balloon enteroscopy and radically resected].

The patient was a 75-year-old woman who had undergone resection of a transverse colon cancer two years before. She had anemia and intestinal obstruction, and a diagnosis of multiple metastases to the small intestine was made by double balloon enteroscopy. Eleven metastatic foci were resected by partial resection of the jejunum and ileum. Adjuvant FOLFOX chemotherapy was given, achieving a 26-month disease-free survival. The double balloon enteroscopy was useful in the definitive diagnosis of this case, and aggressive resection with adjuvant chemotherapy contributed to the good outcome.