An unusual case of primary acinar cell carcinoma of the liver and its treatment.

Acinar cell carcinoma (ACC) is an epithelial neoplasm characterized by morphological features similar to acinar cells found in exocrine glands. Most cases of hepatic ACC reveal evidence of pancreatic exocrine enzyme production and are considered to be metastatic from the pancreas. However, a small number of hepatic ACC cases have been reported in which the tumor is believed to have originated in the liver rather than being a metastatic lesion. In this report we present a case of primary ACC of the liver. A 59-year-old female with no significant past medical history presented with the chief complaint of abdominal pain. A computed tomography (CT) scan of the abdomen showed innumerable mass lesions throughout the liver, initially concerning for metastatic disease. Histopathologic morphology was most consistent with that of ACC, possibly of pancreatic origin. However, the CA 19-9 level was not elevated and no pancreatic lesions were detected on the CT scan. Similar to a previously reported case, the diagnosis of primary ACC of the liver was made based on: acinar cells seen on histology, findings on immunohistochemical staining, radiographic images of liver masses, and the absence of extrahepatic lesions. Previous case reports of primary ACC have differing hypotheses regarding this rare finding. One hypothesis suggests an ectopic origin of acinar cells within the liver. An alternative hypothesis proposes that hepatic and pancreatic cells are ontogenetically derived from a common progenitor cell, which is thought to result in hepatic cells differentiating into acinar cells. The patient was treated with gemcitabine and paclitaxel every 2 weeks for 8 months and then transitioned to every 3 weeks for better tolerance. The patient's symptoms significantly improved within the first 6 weeks of treatment. At the time of the preparation of this report, it has been 17 months since initiation of therapy, and follow-up imaging continues to demonstrate a dramatic decrease in both size and number of hepatic nodules. ACC's are rare tumors that are usually found in glandular tissues. Primary ACC of the liver is extremely rare with only a few cases having been reported. This article adds to the limited literature available on primary hepatic ACC.

Evaluation of factors contributing to the response to fosaprepitant in a heterogeneous, moderately emetogenic chemotherapy population: an exploratory analysis of a randomized phase III trial.

PURPOSE: Fosaprepitant improved prevention of chemotherapy-induced nausea and vomiting (CINV) in a randomized, double-blind phase III trial (PN031). This post hoc analysis explored factors that may have influenced response. METHODS: Adult subjects (N = 1000) scheduled to receive non-anthracycline and cyclophosphamide (AC) moderately emetogenic chemotherapy (MEC) on day 1 were randomly assigned 1:1 to a single-dose, 150-mg intravenous fosaprepitant regimen or a control regimen. Both regimens included dexamethasone and ondansetron on day 1, with ondansetron continuing through day 3 in the control arm only. Complete response (CR; no vomiting and no rescue medication) rates in the acute, delayed, and overall phases (0-25, 25-120, and 0-120 h, respectively) were analyzed by chemotherapy type (carboplatin-based vs non-carboplatin-based), chemotherapy duration (single-day vs multiple-day), and baseline characteristics. RESULTS: Most subjects received single-day chemotherapeutic regimens (70.6%), which were mainly carboplatin-based (67.6%). CR with fosaprepitant was consistent (76-80%) during the delayed and overall phases in carboplatin-based and non-carboplatin-based subgroups and in subgroups receiving single-day or multiple-day MEC regimens. Treatment effects favored fosaprepitant for the carboplatin-based versus the non-carboplatin-based group during the delayed phase (14.1 vs 6.5%; p = 0.06), and for the single-day versus the multiple-day subgroup during the delayed (13.2 vs 3.2%; p = 0.02) and overall phases (12.8 vs 4.0%; p = 0.06). CONCLUSIONS: This exploratory analysis confirms that single-dose fosaprepitant is effective for the prevention of CINV in subjects receiving carboplatin or non-carboplatin in both single- and multiple-day non-AC MEC chemotherapy regimens. This trial is registered at ClinicalTrials.gov , number NCT01594749.

Phase 2 study of two sequential three-drug combinations containing bortezomib, cyclophosphamide and dexamethasone, followed by bortezomib, thalidomide and dexamethasone as frontline therapy for multiple myeloma.

Novel sequential combination therapy for induction may improve the quality of response and therefore prolong survival in newly diagnosed multiple myeloma (MM) patients. We report results from a phase 2 study of two sequential three-drug combinations. Forty-four previously untreated, symptomatic MM patients received: bortezomib 1.3 mg/m(2) (days 1, 4, 8, 11), cyclophosphamide 300 mg/m(2) (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21-day cycles, followed by bortezomib 1.0 mg/m(2), dexamethasone 40 mg and thalidomide 100 mg daily for three cycles. Overall response rate for 42 evaluable patients was 95%, including 19% stringent complete response (sCR), 26% CR, and 57%>/= very good partial response. Twenty-two patients have undergone stem-cell transplantation. After a median follow-up of 20.9 months, five patients have died; none was induction therapy-related. Median event-free survival (EFS) and overall survival (OS) have not been reached; estimated 1-year EFS and OS rates were 81% and 91% respectively. Both three-drug combinations were well tolerated; 82% of patients completed all six cycles. Toxicities were predictable and manageable; the most-commonly reported grade 3/4 toxicity was neuropathy (11%). This novel sequential three-drug combination therapy is effective and well-tolerated in previously untreated MM patients.

Extended follow-up of a phase 2 trial of bortezomib alone and in combination with dexamethasone for the frontline treatment of multiple myeloma.

High-quality response to multiple myeloma (MM) therapy can be predictive for improved outcomes. Novel agents may improve the depth of responses and therefore prolong survival. We report on the extended follow-up of a phase II study in frontline MM of bortezomib alone and in combination with dexamethasone. Forty-nine previously untreated, symptomatic MM patients received bortezomib 1.3 mg/m(2), days 1, 4, 8, 11, for up to six 3-week cycles. High-dose dexamethasone was added for patients not reaching either a partial response after cycle 2 or a complete response (CR) after cycle 4. The overall response rate in 48 evaluable patients was 90%, with 42% achieving at least a very good partial response, of which 19% were CR/near CR. Thirty-six patients received high-dose dexamethasone with 28 (77%) showing improved response. Twenty-seven patients have undergone successful stem-cell transplantation (SCT). After median follow-up of 49 months, 15 patients have died; median overall survival has still not been reached, with an estimated survival at 4 years of 67%. Overall survival with and without SCT was not different (P = 0.54). Grade 3/4 adverse events included neutropenia (10%), sensory neuropathy (6% grade 3), neuropathic pain (4% grade 3), and diarrhoea (4% grade 3). Bortezomib +/- dexamethasone is an effective and well-tolerated induction regimen for the frontline treatment of MM.

Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study.

PURPOSE: Bendamustine hydrochloride is an alkylating agent with novel mechanisms of action. This phase II multicenter study evaluated the efficacy and toxicity of bendamustine in patients with B-cell non-Hodgkin's lymphoma (NHL) refractory to rituximab. PATIENTS AND METHODS: Patients received bendamustine 120 mg/m(2) intravenously on days 1 and 2 of each 21-day cycle. Outcomes included response, duration of response, progression-free survival, and safety. RESULTS: Seventy-six patients, ages 38 to 84 years, with predominantly stage III/IV indolent (80%) or transformed (20%) disease were treated; 74 were assessable for response. Twenty-four (32%) were refractory to chemotherapy. Patients received a median of two prior unique regimens. An overall response rate of 77% (15% complete response, 19% unconfirmed complete response, and 43% partial) was observed. The median duration of response was 6.7 months (95% CI, 5.1 to 9.9 months), 9.0 months (95% CI, 5.8 to 16.7) for patients with indolent disease, and 2.3 months (95% CI, 1.7 to 5.1) for those with transformed disease. Thirty-six percent of these responses exceeded 1 year. The most frequent nonhematologic adverse events included nausea and vomiting, fatigue, constipation, anorexia, fever, cough, and diarrhea. Grade 3 or 4 reversible hematologic toxicities included neutropenia (54%), thrombocytopenia (25%), and anemia (12%). CONCLUSION: Single-agent bendamustine produced durable objective responses with acceptable toxicity in heavily pretreated patients with rituximab-refractory, indolent NHL. These findings are promising and will serve as a benchmark for future clinical trials in this novel patient population.

Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma.

Bortezomib, as a single agent and in combination with dexamethasone, was examined as first-line treatment in 32 consecutive patients with untreated symptomatic multiple myeloma. Patients received bortezomib 1.3 mg/m(2) for a maximum of six 3-week cycles; oral dexamethasone 40 mg was added if a less than partial response (PR) was achieved after two cycles or a less than complete response (CR) was achieved after four cycles. The response rate (CR + PR) was 88%, with undetectable paraprotein (CR) in 6%, and detectable by immunofixation only in 19% [near (n)CR]. All 32 patients completed the first two cycles of bortezomib alone, of whom 3% achieved CR, 9% nCR, and 28% PR. Ten patients received single-agent bortezomib on study, and dexamethasone was added in 22, leading to 15 improved responses. The most common adverse events >/=grade 2 included sensory neuropathy (31%), constipation (28%), myalgia (28%) and fatigue (25%). Sensory neuropathy grade 2 or 3 was reversible within a median of 3 months in five of 10 patients. Bortezomib treatment did not affect stem cell mobilization in eight or transplantation in six patients. Bortezomib alone or in combination with dexamethasone is an effective induction therapy with a high CR and nCR rate and manageable toxicities in previously untreated patients with myeloma.

Docetaxel and carboplatin as first-line therapy in advanced non-small cell lung carcinoma: a phase II study.

BACKGROUND: Taxanes have been widely used against advanced non-small cell lung cancer (NSCLC), alone and in combination with platinum agents. In order to develop a tolerable palliative regimen, we combined carboplatin with low dose docetaxel. PATIENTS AND METHODS: Chemotherapy-naive patients, with Stage IIIB or IV NSCLC and an ECOG performance status < or = 2, were enrolled. Treatment consisted of docetaxel 60 mg/m2 and carboplatin AUC 6 every 21 days. Therapy continued for 1 year or 6 months beyond best response, whichever was greater. RESULTS: Twenty-five patients were enrolled. Most patients (80%) had Stage IV disease. The partial response rate was 16%. Response duration ranged from 6 to 115 weeks. Median survival was 55 weeks. Toxicity was generally limited to grade 3 or 4 neutropenia. There was 1 septic death. CONCLUSION: Survival compared favorably to other similar trials employing higher doses of docetaxel. Additionally, a hematologic toxicity advantage was seen compared to regimens containing higher doses of docetaxel.