Comparisons of Clinical Outcomes in Women with Advanced Ovarian Cancer Treated with Frontline Intraperitoneal versus Dose-Dense Platinum/Paclitaxel Chemotherapy without Bevacizumab.

Background: We aimed to compare the clinical outcomes between intraperitoneal chemotherapy and dose-dense chemotherapy for the frontline treatment of advanced ovarian, fallopian tube and primary peritoneal cancer in women not receiving bevacizumab. Methods: All consecutive women with stage II~IV cancer treated with either frontline intraperitoneal or dose-dense platinum/paclitaxel chemotherapy and not receiving bevacizumab between March 2006 and June 2019 were reviewed. Results: A total of 50 women (intraperitoneal group, n = 22; dose-dense group, n = 28) were reviewed. Median progression-free survival (32.6 months versus 14.2 months; adjusted hazard ratio = 0.38; 95% CI = 0.16 to 0.90, p = 0.03) and overall survival (not reached versus 30.7 months; adjusted hazard ratio = 0.23, 95% CI = 0.07 to 0.79, p = 0.02) were significantly higher in the intraperitoneal group than in the dose-dense group. A multivariable Cox proportional-hazards model also indicated that the number of frontline chemotherapy cycles (adjusted hazard ratio = 0.66, 95% CI 0.47 to 0.94, p = 0.02) was a predictor of better overall survival. Nausea/vomiting and nephrotoxicity occurred more frequently in the intraperitoneal group (p = 0.02 and <0.0001, respectively). Conclusions: Intraperitoneal chemotherapy seems to be superior in progression free survival and overall survival to dose-dense chemotherapy in the frontline treatment of women with optimally resected advanced ovarian, fallopian tube or primary peritoneal cancer and not receiving bevacizumab.

Gemcitabine plus cisplatin for patients with recurrent or metastatic nasopharyngeal carcinoma in Taiwan: a multicenter prospective Phase II trial.

OBJECTIVE: This multicenter Phase II trial evaluated the toxicity/efficacy of gemcitabine plus cisplatin as first-line chemotherapy in patients with recurrent/metastatic nasopharyngeal carcinoma. METHODS: Gemcitabine 1250 mg/m(2) on Days 1 and 8 and cisplatin 75 mg/m(2) on Day 1 were administered at a 3-week interval. The primary endpoint was the response rate. Secondary endpoints included progression-free survival, overall survival, response duration and safety. RESULTS: Fifty-two patients were recruited between 2004 and 2008. The response rate was 51.9% (complete remission rate, 9.6%) in the intent-to-treat group. The median progression-free and overall survivals were 9.8 and 14.6 months, respectively. The major Grade III/IV adverse event was leucopenia (61.6%). The mean number of cycles was 6.63 ± 0.40. The regimen was well-tolerated, although one treatment-related death occurred after severe sepsis from aspiration pneumonia. CONCLUSIONS: Gemcitabine plus cisplatin is an effective, well-tolerated regimen as a first-line treatment for recurrent/metastatic nasopharyngeal carcinoma.

ß-catenin (CTNNB1) mutations are not associated with prognosis in advanced hepatocellular carcinoma.

OBJECTIVES: Mutation of the exon 3 of CTNNB1, the coding gene of ß-catenin, is a crucial molecular mechanism leading to aberrant activation of the Wnt/ß-catenin pathway, which is highly associated with the carcinogenesis of hepatocellular carcinoma (HCC). The prevalence and clinical significance of CTNNB1 mutations in advanced HCC remain unclear. METHODS: Patients with advanced HCC and available pathologic tissues (either obtained when diagnosed at advanced or early stages) were enrolled in this study. Direct sequencing of exon 3 of CTNNB1 was performed to detect somatic mutations. The associations between CTNNB1 mutations and clinicopathologic features were analyzed. RESULTS: A total of 115 patients were enrolled, among whom 78 (67.8%) had chronic hepatitis B virus infection. Twenty-one (18.3%) patients were found to have CTNNB1 mutations, all of which were missense mutations. The CTNNB1 mutation rates were similar among pathologic tissues obtained at advanced and early stages (17.5 and 20.0%, respectively). Patients aged over 60 years were more likely to have CTNNB1 mutations than patients younger than 60 years (32.6 vs. 8.7%, p = 0.001). The mutations were not associated with survival or other clinicopathologic features. CONCLUSION: In patients with advanced HCC, CTNNB1 mutations were not prognostically significant. No apparent increase of CTNNB1 mutations occurred during the progression of HCC.

Efficacy, safety, and potential biomarkers of thalidomide plus metronomic chemotherapy for advanced hepatocellular carcinoma.

OBJECTIVES: Thalidomide has been shown to have antitumor activity in some patients with advanced hepatocellular carcinoma (HCC). We initiated a phase II study to determine the safety and efficacy of adding metronomic chemotherapy to thalidomide as first-line therapy. METHODS: This open- labeled, single-arm, multicentered, investigator-initiated study enrolled patients with treatment-naïve advanced HCC not amenable to locoregional therapies. Treatment included oral thalidomide (100 mg twice daily) and tegafur/uracil [125 mg/m(2) (based on tegafur) twice daily]. Tumor assessment was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Pretreatment plasma levels of angiogenesis factors were correlated with patient outcomes. RESULTS: Forty-three patients were included. Sixteen (37%) patients had a Cancer of the Liver Italian Program (CLIP) score of 4, and 31 (72%) patients had chronic hepatitis B virus infection. The objective response rate was 9%, and the disease stabilization rate was 33%. The median progression-free survival was 1.9 months (95% CI 1.7-2.1 months), and the median OS was 4.6 months (95% CI 2.3-6.9 months). Treatment was generally tolerable. High baseline plasma levels of interleukin (IL)-6 and IL-8 were adversely correlated with patient survivals. CONCLUSIONS: The combination of thalidomide and tegafur/uracil was safe and demonstrated modest activity in patients with advanced HCC.

Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma.

BACKGROUND: To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC). METHODS: Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction. RESULTS: After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively. CONCLUSION: HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings.

Intensity modulated radiotherapy for elderly bladder cancer patients.

BACKGROUND: To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer. METHODS: From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field "box" pelvic radiation therapy (2DRT) plans were generated for comparison. RESULTS: The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% vs .37.5%, respectively; the corresponding values for disease-free survival were 58.3% vs. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% vs. 83.3%, respectively; and for metastases-free survival, the values were 66.7% vs. 60.0%, respectively. The 2-year OS rates for T1, 2 vs. T3, 4 were 66.7% vs. 35.4%, respectively (p = 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, p = 0.004). CONCLUSION: IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate.

Concurrent chemoradiotherapy with helical tomotherapy for oropharyngeal cancer: a preliminary result.

PURPOSE: To review the experience with and evaluate the treatment plan for helical tomotherapy for the treatment of oropharyngeal cancer. METHODS AND MATERIALS: Between November 1, 2006 and January 31, 2009, 10 histologically confirmed oropharyngeal cancer patients were enrolled. All patients received definitive concurrent chemoradiation with helical tomotherapy. The prescription dose to the gross tumor planning target volume, the high-risk subclinical area, and the low-risk subclinical area was 70 Gy, 63 Gy, and 56 Gy, respectively. During radiotherapy, all patients were treated with cisplatin, 30 mg/m(2), plus 5-fluorouracil (425 mg/m(2))/leucovorin (30 mg/m(2)) intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. Several parameters, including maximal or median dose to critical organs, uniformity index, and conformal index, were evaluated from dose-volume histograms. RESULTS: The mean survival was 18 months (range, 7-22 months). The actuarial overall survival, disease-free survival, locoregional control, and distant metastasis-free rates at 18 months were 67%, 70%, 80%, and 100%, respectively. The average for uniformity index and conformal index was 1.05 and 1.26, respectively. The mean of median dose for right side and left side parotid glands was 23.5 and 23.9 Gy, respectively. No Grade 3 toxicity for dermatitis and body weight loss and only one instance of Grade 3 mucositis were noted. CONCLUSION: Helical tomotherapy achieved encouraging clinical outcomes in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable, even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings.

Cardiac magnetic resonance imaging in sunitinib malate-related cardiomyopathy: no late gadolinium enhancement.

Sunitinib malate, an oral multitargeted tyrosine kinase inhibitor (TKI), has been approved for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumors. It is supposed that this targeted approach improves antitumor activity with less toxicity than traditional chemotherapy. However, unanticipated cardiotoxicity related to TKIs has been reported. Less well described are the treatment and prognosis of patients with sunitinib-related cardiogenic shock. Here, we report a successfully treated case. In contrast to previous case reports, the shock status did not allow for standard heart failure treatment with angiotensin-converting enzyme inhibitor or beta-blocker. We used intra-aortic balloon counterpulsation, and the patient survived. Twenty-four days after onset, the patient's left ventricular ejection fraction had improved from 20% to 48%. To the best of our knowledge, this is the first case report of severe heart failure after sunitinib treatment in Taiwan. As the clinical application of TKIs expands, cardiologists and oncologists should be alert to the possible adverse cardiovascular effects and be ready to institute prompt treatment.

High-dose tamoxifen modulates drug resistance to doxorubicin, dacarbazine and ifosfamide in metastatic uterine leiomyosarcoma.

A 46-year-old female patient suffered from uterine malignant leiomyosarcoma. Ten months after abdominal subtotal hysterectomy, multiple lung, bone and spine metastases developed. She received 3 cycles of infusional ADI chemotherapy (adriamycin 60 mg/m2, 96-hour i.v. infusion, dacarbazine 500 mg/m2, 96-hour i.v. infusion and ifosfamide 5,000 mg/m2, 72-hour i.v. infusion, repeated every 3 weeks), but the metastatic tumors progressed. An empirical ADI-TAM chemotherapy which incorporated high-dose tamoxifen (TAM) (150 mg/m2/day, in 4 divided doses) into the original ADI regimen was applied from the fourth cycle. High-dose tamoxifen consisted of 240 mg/day for 4 days during chemotherapy and 40 mg/day between cycles. Good partial response with nearly total tumor reduction was achieved after 3 cycles of ADI-TAM therapy. The excellent tumor response by simple addition of high-dose tamoxifen into a previously inactive ADI regimen advocates further investigation for the development of chemotherapy in metastatic uterine leiomyosarcoma.

High incidence of CD56 expression and relapse rate in acute myeloid leukemia patients with t(8;21) in Taiwan.

BACKGROUND AND PURPOSE: CD56 is a marker of natural killer cells, but can also be found on blast cells in acute myeloid leukemia (AML). The prognostic implications of CD56 expression in AML are not clear. In this study, we evaluated the correlation among CD56 expression, cytogenetic abnormality, and clinical outcome in AML. METHODS: CD56 expression was analyzed in leukemic cells from 94 adults with primary AML in Taiwan and was correlated with clinical and hematologic features, cytogenetics, and immunophenotypes of the leukemia. RESULTS: Thirty patients (32%) showed CD56 expression. CD56+ AML patients had a higher lactate dehydrogenase level than CD56- patients (1.136 vs 730 V/L, p = 0.048). Patients with t(8;21) had a significantly higher incidence (89%, 8/9) of CD56 positivity in leukemic cells than those with normal karyotype or other cytogenetic abnormalities (26%, 22/85, p < 0.001). In general, there was no difference in overall survival time in CD56+ and CD56- AML patients. However, three patients had central nervous system involvement at initial presentation; two of these had concomitant CD56 expression and t(8;21). In addition, five of the seven patients with t(8;21) and CD56 expression who achieved complete remission later relapsed. CONCLUSIONS: The incidence of CD56 expression in AML patients with t(8;21) is very high in Taiwan, and it may imply a poor prognosis in this subgroup of patients.