Multicenter phase II study on cisplatin, pemetrexed, and bevacizumab followed by maintenance with pemetrexed and bevacizumab for patients with advanced or recurrent nonsquamous non-small cell lung cancer: MAP study.

BACKGROUND: We evaluated the safety and efficacy of induction chemotherapy with bevacizumab followed by maintenance chemotherapy with bevacizumab for advanced non-small cell lung cancer (NSCLC) in this multicenter phase II study. METHODS: Chemotherapy-naïve patient with stage IIIB-IV or recurrent nonsquamous NSCLC were eligible. We planned approximately four cycles of induction cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) followed by maintenance with pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) until disease progression. Progression-free survival (PFS) was the primary endpoint. RESULTS: Forty patients received a median of four induction chemotherapy cycles. Of them, 35 (87.5%) patients received a median of nine maintenance chemotherapy cycles. The objective response was 70.6%, and the disease control rate was 97.1%. The median PFS was 10.8 (95% CI, 9.0-12.6), and overall survival was 48.0 (95% CI, 32.9-63.1) months. Median PFS of 23 patients with epidermal growth factor receptor (EGFR) mutations and of 16 patients without EGFR mutations were 12.9 (95% CI, 9.4-16.3) and 7.9 (95% CI, 1.1-14.7) months, respectively. Toxicities graded ≥3 included neutropenia (15%), anemia (15%), hypertension (7.5%), anorexia (7.5%), fatigue (7.5%), thromboembolic events (5%), jaw osteonecrosis (5%), nausea (2.5%), oral mucositis (2.5%), tumor pain (2.5%), hyponatremia (2.5%), and gastrointestinal perforation (2.5%). Treatment-related deaths were not found. CONCLUSIONS: In patients with advanced or recurrent nonsquamous NSCLC, induction chemotherapy with cisplatin, pemetrexed, and bevacizumab followed by maintenance chemotherapy with pemetrexed and bevacizumab is safe and effective regardless of their EGFR mutation status. TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000005569 . Registered date: May 8, 2011.

[A case of triple-negative breast cancer responding to multidisciplinary treatment containing bevacizumab].

We report a case of a 64-year-old woman with Stage IV breast cancer who responded well to chemotherapy containing bevacizumab. She noticed a left breast tumor with acute progression and was diagnosed as having Stage IV, estrogen receptor( ER)(-), progesterone receptor(PgR)(-), human epidermal growth factor receptor 2(HER2)(-)breast cancer (T4cN3cM1[lymph nodes]). She received 5 courses of adriamycin(60mg/m / 2)plus cyclophosphamide(600mg/m2)(AC therapy)and 4 courses of weekly paclitaxel(PTX 90mg/m / 2)plus bevacizumab(AVA 10 mg/m2)as systemic therapy. Computed tomography(CT)and magnetic resonance imaging(MRI)revealed a complete response(CR). After local resection of the breast tumor and radiation to the breast and regional lymph nodes, capecitabine therapy was initiated. Currently, at 5 months after surgery, no new lesion has been detected.

[Three cases of cancer-related pain for which oxycodone injection was efficacious].

The intravenous or subcutaneous route is a useful option for administering opioids when cancer patients with moderate to severe pain are unable to take oral medication. An injectable form of oxycodone is now available, and three patients with cancer-related pain were treated successfully with continuous intravenous or subcutaneous oxycodone. The first case showed transient switching from oral oxycodone to the parenteral form during the active treatment phase, resulting in satisfactory pain management. The second case suggested that oxycodone may have a more favorable analgesic profile in severe neuropathic cancer pain compared with fentanyl. Finally, the third case demonstrated that oxycodone injection is relatively safe for renal-impaired patients.

Real-world experience of tropomyosin receptor kinase inhibition with entrectinib in ETV6-NTRK3 positive metastatic salivary secretory carcinoma: A case series.

BACKGROUND: The efficacy of entrectinib, a potent inhibitor of tropomyosin receptor kinases, c-ros oncogene 1, and anaplastic lymphoma kinase has been demonstrated in neurotrophic receptor tyrosine kinase fusion-positive pediatric and adult solid tumors. However, real-world data on entrectinib therapy for salivary gland malignancies are limited. METHODS: We describe a multicenter case series of four consecutive patients with ETV6-NTRK3 fusion-positive metastatic salivary secretory carcinoma (SSC) treated with entrectinib. RESULTS: All patients had a prior history of systemic therapy with cytotoxic chemotherapy or immune checkpoint inhibitors. All patients achieved durable radiographic complete response. Adverse events included weight gain, dizziness, increase in creatine kinase level, and withdrawal pain, but were manageable by the interruption and dose reduction of entrectinib. CONCLUSION: Durable complete response was achieved with entrectinib in patients with ETV6-NTRK3 fusion-positive metastatic SSC. The clinical benefit of entrectinib supports the importance of routine screening for NTRK gene fusion in patients with SSC.

Comprehensive genomic profiling of Japanese patients with thoracic malignancies: A single-center retrospective study.

BACKGROUND: Few studies have been conducted on comprehensive genomic profiling (CGP) panels in Japanese patients with thoracic malignancies after completing standard treatment. Consequently, its value in clinical practice remains unclear. METHODS: We conducted a retrospective study of Japanese patients with thoracic malignancies who underwent CGP between June 2019 and November 2022 at our hospital. We evaluated the detection rate of actionable genetic alterations and percentage of patients who received genomically-matched therapy. Furthermore, we examined the value of the CGP panel in patients who underwent multiplex gene-panel testing prior to their initial treatment. This study was performed in accordance with the principles of the Declaration of Helsinki. RESULTS: The study included 56 patients, of whom 47 (83.9%) had actionable genetic alterations and 8 (14.3%) received genomically-matched therapy. Of these, four patients were treated with approved drugs and three patients were treated with investigational agents. In addition, one patient was treated with approved drugs using the patient-directed care system. Of the 17 patients who had multiplex gene-panel testing performed at the start of their initial therapy, two (11.8%) were newly identified by the CGP panel and subsequently received genomically-matched therapy. EGFR L718Q and MET amplification were observed in two of the seven patients with epidermal growth factor receptor-tyrosine kinase inhibitor resistance. CONCLUSIONS: The CGP panel could identify genetic alterations, thereby facilitating genomically-matched therapy, even in patients with thoracic malignancies who could not be identified using multiplex gene-panel testing.

Efficacy of probiotics and trimebutine maleate for abemaciclib-induced diarrhea: A randomized, open-label phase II trial (MERMAID, WJOG11318B).

BACKGROUND: Abemaciclib-induced diarrhea (AID) impairs quality of life (QOL) and treatment adherence in patients with breast cancer. Supportive treatment with loperamide is associated with constipation. We hypothesized that probiotics and trimebutine maleate (TM) would decrease the frequency of AID without causing constipation. METHODS: Hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer patients were randomized into the probiotic Bifidobacterium (A) or probiotic Bifidobacterium and TM (B) groups. Endocrine therapy, Abemaciclib and probiotic Bifidobacterium three times a day for 28 days, was administered to both arms. Arm B was treated with TM upon the onset of diarrhea. The primary endpoint was the percentage of patients who experienced grade ≥2 diarrhea. The secondary endpoints were safety, frequency, and duration of all-grade diarrhea; frequency of emesis and constipation; usage of loperamide; and health-related QOL/patient-reported outcome during the study. We evaluated whether the primary endpoint of each arm exceeded the predetermined threshold. RESULTS: Fifty-one patients completed treatment. Grade 2 diarrhea occurred in 52% and 50% of patients in Arm A and Arm B, respectively. One patient experienced grade 3 diarrhea in each arm. The median duration of grade2 diarrhea was 2 and 2.5day, and only one patient required dose reduction. Grade ≥2 constipation was observed in 4% of Arm A and 3.6% of Arm B. CONCLUSIONS: Probiotic Bifidobacterium or the combination of probiotic Bifidobacterium with TM did not decrease the incidence of grade 2 or greater diarrhea compared with historical control, although the grade 3 or greater diarrhea was reduced. CLINICAL TRIAL REGISTRATION: jRCT (Japan registry of clinical trials). jRCTs031190154.

Bleomycin-induced pulmonary fibrosis after tumor lysis syndrome in a case of advanced yolk sac tumor treated with bleomycin, etoposide and cisplatin (BEP) chemotherapy.

Ovarian yolk sac tumor (YST) is a highly aggressive malignancy arising in young women. Chemotherapy has dramatically improved the prognosis, and bleomycin, etoposide, and cisplatin (BEP) combination chemotherapy appears to be the most effective combination regimen. A 23-year-old woman was admitted to our hospital with worsening abdominal distention and a lower abdominal mass. She was diagnosed with a stage IIIc pure YST of the right ovary, and right salpingo-oophorectomy was performed; there were numerous disseminated peritoneal tumors within the abdominal cavity. A few days postoperatively, massive ascites developed, and right hydronephrosis occurred. Chemotherapy with BEP was started, and after 24 h of administration, oliguria and tumor lysis syndrome (TLS) developed. Continuous hemodiafiltration was started, and hemodialysis was initiated following full-dose standard cisplatin and etoposide on days 2-5 of the 1st cycle. After the electrolyte abnormalities and the elevation of creatinine became normal, the patient received an additional three cycles of BEP and achieved complete remission. However, she also suffered from severe non-hematological toxicities, including grade 3 left ventricular dysfunction and grade 4 pulmonary fibrosis. In the case of rapidly progressing and high-volume YST treated with BEP chemotherapy, special attention should be paid to bleomycin-induced pulmonary toxicity following TLS. Further study is required to optimize drug exposure to ensure efficacy and reduce the risk of side effects in this population.

Effect of mustard gas exposure on incidence of lung cancer: a longitudinal study.

Sulfur mustard, an agent used in chemical warfare, is an alkylating substance with carcinogenic potential. However, the precise long-term carcinogenic effects of mustard gas are unclear. Since 1952, the authors have conducted health surveys of former workers who were employed from 1929 to 1945 in a poisonous gas factory in Okuno-jima, Hiroshima, Japan. This prospective study was undertaken from 1952 to 2005 to examine the incidence of lung cancer among the workers who were exposed to mustard gas (n=480), lewisite (n=55), and/or diphenylcyanarsine (n=178), as well as the incidence among unexposed workers (n=969). The stochastic relation between exposure and lung cancer was explored on the basis of multistage carcinogenesis by using an accelerated hazard model with a transformed age scale. Mustard gas exposure was found to transform the age scale for developing lung cancer. One year of exposure in subjects ≤18 or >18 years old at first exposure shifted the age scale down by 4.9 years and 3.3 years, respectively. On the basis of the long-term follow-up of former workers in the poisonous gas factory, the authors concluded that sulfur mustard decreased the age at which people were at risk of developing lung cancer and that the effect declined with aging.

[A case of germ-cell tumor of the mediastinum].

An 18-year-old man complaining of chest pain was admitted to our hospital. Contrast-enhanced chest computed tomography (CT) showed an anterior mediastinal tumor with patchy enhanced lesions in the peripheral and poorly-enhanced central areas. His serum alpha fetoprotein (AFP) level was high. FDG-PET imaging indicated intense FDG uptake in the mediastinal tumor (SUVmax was 11.2), but no other abnormal FDG uptake, including in his testes, was detected. CT-guided needle biopsy revealed necrotizing tissue, including immature cartilage-like tissue. Based on these clinical features, we diagnosed mixed-type germ cell tumor originating from the mediastinum. Bleomycin, etoposide and cisplatin combination chemotherapy was administered every 3 weeks, for 4 cycles. His serum AFP level declined during the treatment course, and the mediastinal tumor decreased in size. After 4 cycles of chemotherapy, the residual tumor was resected completely and no viable cells were detected in the resected tumor. Tumor recurrence has not been detected for more than 9 months after surgery without adjuvant chemotherapy at the time of writing.

[mFOLFOX6 for treatment of anal canal cancer with disseminated carcinomatosis of bone marrow--a case report].

A 66-year-old man was referred to our hospital because of a two-week history off ever and low back pain. There was a hard anal mass on rectal examination. Colonoscopy and computed tomography showed anal adenocarcinoma, multiple metastases to lymph nodes and bones. Blood test showed severe disseminated intravascular coagulation (DIC). Microscopic examination of the bone marrow aspirate revealed disseminated carcinomatosis of the bone marrow. Systemic chemotherapy (mFOLFOX6) was started, then remission of DIC and shrinkage of the tumor were observed. Although the patient had cerebral infarction during the first course of chemotherapy, he received nine courses of treatment. He died six months later because of cerebellar hemorrhage.