Primary Testicular Mucinous Adenocarcinoma-a Case Report and Review of Literature.

Testicular tumors include germ cell tumors, sex cord stromal tumors, and ovarian type epithelial tumors. Testicular mucinous tumors belong to ovarian type epithelial tumors and are extremely rare with only 31 cases reported in literature so far. Among those, mucinous adenocarcinoma constitutes only 9 cases. There are no standard treatment guidelines owing to their rarity. We report a case of primary testicular mucinous adenocarcinoma managed by orchidectomy, chemotherapy, and retroperitoneal lymph node dissection. A 44-year-old gentleman presented with right testicular tumor with infiltration and ulceration of scrotal skin. Tumor markers were within normal limits. Patient underwent orchidectomy with excision of involved scrotal skin. HPE suggested mucinous adenocarcinoma of testis. Patient was then administered chemotherapy but had progression of disease and hence taken up for retroperitoneal, bilateral pelvic, and bilateral inguinal lymph node dissection with revision of spermatic cord. Patient recovered uneventfully and is on regular follow-up 6 months now since surgery. There are no standard guidelines for the management of mucinous adenocarcinoma of testis. It is essential to rule out mucinous carcinoma of gastrointestinal tract metastasizing to testis before labeling as primary mucinous adenocarcinoma of testis. Surgery remains the mainstay of treatment in metastasis confined to retroperitoneal and inguinal lymph nodes. Further studies are needed to identify optimal chemotherapy regimen for metastatic and adjuvant scenarios.

A phase 1b, multicenter, open-label, dose-finding study of eribulin in combination with carboplatin in advanced solid tumors and non-small cell lung cancer.

PURPOSE: This phase 1b study investigated the maximum tolerated dose (MTD; primary objective), safety, pharmacokinetics, and antitumor activity (secondary objectives) of eribulin combined with carboplatin in patients with solid tumors and, in particular, non-small cell lung cancer (NSCLC). METHODS: Two dose-escalation schemes were evaluated with carboplatin, at an area under the curve (AUC) of either 5 or 6 mg/mL·min. Eribulin, dose-escalated from 0.7 to 1.4 mg/m2 was administered 1 h before (Schedule A) or after (Schedule B) carboplatin as a 2-5-min bolus infusion on days 1 and 8 of a 21-day cycle. Following tolerability assessment, patients with NSCLC were recruited in an expansion cohort. RESULTS: The MTDs were eribulin 1.4 and 1.1 mg/m2 with carboplatin AUC 5 and AUC 6, respectively. The latter combination was used to treat NSCLC patients in the expansion cohort. Pharmacokinetics of eribulin and carboplatin were generally unaffected by administration sequence (i.e., administration of carboplatin did not significantly affect eribulin Cmax and AUC0-t and the converse was also observed). In the NSCLC cohort, the objective response rate was 27%. Median overall and progression-free survival durations were 12.1 and 4.2 months, respectively. No unexpected safety findings were observed. CONCLUSIONS: The combination of eribulin and carboplatin demonstrated antitumor activity; however, recent therapeutic advances may be more promising approaches for first-line treatment of NSCLC. Clinical trial registration NCT00268905.

Occipital Condyle Syndrome Caused by Isolated Bone Metastases from Thyroid Cancer.

Occipital condyle syndrome is a rare cause of pain in the head which is characterized by severe and persistent unilateral suboccipital headache with unilateral hypoglossal nerve palsy. We report an elderly female who presented with dysarthria and suboccipital headache. On further evaluation, she was found to have a solitary bone metastases from thyroid cancer. She was treated with local radiation therapy for pain relief, total thyroidectomy, and high-dose radioiodine therapy. The patient is presently free of pain with very good control of the thyroid cancer status.

Functional Genomic Investigation of the Molecular Biological Impact of Electron Beam Radiation in Lymphoma Cells.

PURPOSE: The biological response of electron beam radiation (EBR) in tumors remains underexplored. This study describes the molecular biological and genomic impact of EBR on tumor cells. METHODS: A mouse model bearing Dalton's lymphoma ascites cells was exposed to an 8-MeV pulsed electron beam, at a dose rate of 2 Gy/min using a microtron, a linear accelerator. The radiation-induced changes were assessed by histopathology, fluorescence-activated cell sorting, signaling pathway-focused reporter assays, and gene expression by microarray analysis. RESULTS: EBR was found to increase apoptosis and G2-M cell cycle arrest with concomitant tumor regression in vivo. The microarray data revealed that EBR induced tumor regression, apoptosis, and cell cycle arrest mediated by p53, PPAR, and SMAD2/3/4 signaling pathways. Activation of interferon regulatory factor and NFkB signaling were also found upon EBR. Chemo-genomics exploration revealed the possibility of drugs that can be effectively used in combination with EBR. CONCLUSION: For the first time, an 8-MeV pulse EBR induced genomic changes, and their consequence in molecular and biological processes were identified in lymphoma cells. The comprehensive investigation of radiation-mediated responses in cancer cells also revealed the potential therapeutic features of EBR.

Eltrombopag with gemcitabine-based chemotherapy in patients with advanced solid tumors: a randomized phase I study.

Preventing chemotherapy-induced thrombocytopenia could avoid chemotherapy dose reductions and delays. The safety and maximum tolerated dose of eltrombopag, an oral thrombopoietin receptor agonist, with gemcitabine-based therapy was evaluated. Patients with advanced solid tumors and platelets ≤300 × 10(9) /L receiving gemcitabine plus cisplatin or carboplatin (Group A) or gemcitabine monotherapy (Group B) were randomized 3:1 to receive eltrombopag or placebo at a starting dose of 100 mg daily administered on days -5 to -1 and days 2-6 starting from cycle 2 of treatment. Nineteen patients (Group A, n = 9; Group B, n = 10) received eltrombopag 100 mg and seven (Group A, n = 3; Group B, n = 4) received matching placebo. Nine eltrombopag patients in Group A and eight in Group B had 38 and 54 occurrences of platelet counts ≥400 × 10(9) /L, respectively. Mean platelet nadirs across cycles 2-6 were 115 × 10(9) /L and 143 × 10(9) /L for eltrombopag-treated patients versus 53 × 10(9) /L and 103 × 10(9) /L for placebo-treated patients in Groups A and B, respectively. No dose-limiting toxicities were reported for eltrombopag; however, due to several occurrences of thrombocytosis, a decision was made not to dose-escalate eltrombopag to >100 mg daily. In Groups A and B, 14% of eltrombopag versus 50% of placebo patients required chemotherapy dose reductions and/or delays for any reason across cycles 3-6. Eltrombopag 100 mg once daily administered 5 days before and after day 1 of chemotherapy was well tolerated with an acceptable safety profile, and will be further tested in a phase II trial. Fewer patients receiving eltrombopag required chemotherapy dose delays and/or reductions compared with those receiving placebo.

Efficacy and safety of fentanyl pectin nasal spray compared with immediate-release morphine sulfate tablets in the treatment of breakthrough cancer pain: a multicenter, randomized, controlled, double-blind, double-dummy multiple-crossover study.

BACKGROUND: Immediate-release morphine sulfate (IRMS) remains the standard treatment for breakthrough cancer pain (BTCP), but its onset of effect does not match the rapid onset and short duration of most BTCP episodes. OBJECTIVE: This study will evaluate the efficacy/tolerability of fentanyl pectin nasal spray (FPNS) compared with IRMS for BTCP. METHODS: Patients (n = 110) experiencing one to four BTCP episodes/day while taking ≥ 60 mg/day oral morphine (or equivalent) for background cancer pain entered a double-blind, double-dummy (DB/DD), multiple-crossover study. Patients completing a titration phase (n = 84) continued to a DB/DD phase: 10 episodes of BTCP were randomly treated with FPNS and oral capsule placebo (five episodes) or IRMS and nasal spray placebo (5 episodes). The primary end point was pain intensity (P < .05 FPNS vs. IRMS) difference from baseline at 15 minutes (PID(15)). Secondary end points were onset of pain intensity (PI) decrease (≥ 1-point) and time to clinically meaningful pain relief (CMPR, ≥ 2-point PI decrease). Safety and tolerability were evaluated by adverse events (AEs) and nasal assessments. By-patient and by-episode analyses were completed. RESULTS: Compared with IRMS, FPNS significantly improved mean PID(15) scores. 57.5% of FPNS-treated episodes significantly demonstrated onset of PI improvement by 5 minutes and 95.7% by 30 minutes. CMPR (≥ 2-point PI decrease) was seen in 52.4% of episodes by 10 minutes. Only 4.7% of patients withdrew from titration (2.4% in DB/DD phase) because of AEs; no significant nasal effects were reported. CONCLUSION: FPNS was efficacious and well tolerated in the treatment of BTCP and provided faster onset of analgesia and attainment of CMPR than IRMS.