Chi-Ting Liau

WEEKLY 24 H INFUSION OF HIGH-DOSE 5-FLUOROURACIL AND LEUCOVORIN IN PATIENTS WITH BILIARY TRACT CARCINOMAS

From October 1995 to June 1997, 19 chemotherapy-naive patients with pathology-proven locally advanced or metastatic biliary tract carcinomas (BTC) were enrolled. The regimen consisted of 5-fluorouracil (5-FU) 2600 mg/m2 and leucovorin (LV) 150 mg by weekly 24 h infusion for 6 weeks and followed by a 2 week break. The treatment was terminated if disease progressed, the patient refused or unacceptable toxicity occurred. All patients required a Port-A catheter insertion and were treated at outpatient clinics by portable infusion pumps. There were 12 males and seven females with a median age of 62 years (range 45-77). The primary tumor sites were nine intrahepatic cholangiocarcinomas (CC), three perihilar CC, one distal BTC and six gallbladder cancers. A total of 179 chemotherapy sessions were given with a mean of 9.5 (range 2-18). Eighteen patients were evaluable for response. The response rates were: 33% (six of 18) partial response (PR), 39% (seven of 18) stable disease (SD) and 28% (five of 18) progressive disease (PD). All of the patients were evaluable for toxicity. The most common toxicities were mild fatigue (nine of 19, 47%), loss of appetite (nine of 19, 47%), skin hyperpigmentation (five of 19, 26%) and diarrhea (two of 19, 11%). Only one patient had grade IV myelotoxicity with sepsis but without treatment-related death. The median time to progression was 4 months. The overall median survival time was 7.0 months. The median survival time of the PR was not reached, SD was 8.0 months and PD 3.5 months. In conclusion, weekly high-dose 5-FU with LV by 24 h infusion in an outpatient setting for patients with BTC is effective, only mildly toxic and deserves further study.

Mitomycin C with weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with biliary tract and periampullar carcinomas.

We have reported a 33% partial response rate with acceptable toxicity using weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in patients with far advanced biliary tract cancers (BTC). In this study, we added mitomycin (MMC) to 5-FU and LV in an attempt to improve the response rate and survival. From July 1997 to September 1999, 25 chemotherapy-naive patients with pathology-proven far advanced BTC and periampullar cancers were enrolled. The regimen consisted of MMC 10 mg/m2 every 8 weeks combined with 5-FU 2600 mg/m2 and LV 150 mg at a schedule of 24-h infusion weekly for 6 weeks followed by a 2 week break. There were 10 males and 15 females with a median age of 57 years (range 40-76). The sites of primary tumor were 15 intrahepatic cholangiocarcinomas (CC), one perihilar CCs, three distal BTC, three gallbladder cancers (GB) and three periampular cancers. A total of 148 sessions of chemotherapy were given with a mean of 8 (range 2-18). Nineteen patients were evaluable for response. The response rate was: 26% (five of 19) partial response, 42% (eight of 19) stable disease and 32% (six of 19) progressive disease. All of the patients were evaluable for toxicity. Toxicities more than grade III-IV were thrombocytopenia 16% (four of 25), leukopenia 12% (three of 25) and vomiting 4% (one of 25). There were four treatment-related deaths. The median time to disease progression was 3 months. The median survival was 6 months. A combination of MMC with weekly high-dose 5-FU and LV in patients with BTC did not improve the response rate, but produced more toxicity than weekly high-dose 5-FU and LV alone.

Oral bioavailability of a novel paclitaxel formulation (Genetaxyl) administered with cyclosporin A in cancer patients

The formulation excipient Cremophor EL (CrEL) is known to limit the absorption of oral paclitaxel given together with cyclosporin A. We hypothesized that the use of oral Genetaxyl, a paclitaxel formulation containing only 20% CrEL would have an improved oral bioavailability. Cohorts of six patients were treated with oral Genetaxyl at a dose of 60, 120, or 180 mg/m2 and 10 mg/kg of oral cyclosporin A in cycle 1. In cycle 2, patients received intravenous (i.v.) Genetaxyl (175 mg/m2, 3-h infusion). Three additional patients received one dose of generic i.v. paclitaxel (Genaxol, containing 50% CrEL; 175 mg/m2, 3-h infusion). The median area under the plasma concentration–time curve (AUC) and peak concentration of total paclitaxel following i.v. Genetaxyl were lower than those for i.v. Genaxol, as a result of significantly increased clearance (P=0.017), and the AUC ratio for unbound to total paclitaxel for i.v. Genetaxyl was about two times higher than that for i.v. Genaxol (P=0.0077). After oral administration of Genetaxyl at doses of 60, 120, and 180 mg/m2, the median total paclitaxel AUCs were 1.29, 1.60, and 1.85 μg×h/ml, respectively, suggesting a less than proportional increase in systemic exposure with increasing doses. The corresponding median values for the apparent bioavailability of oral Genetaxyl were similar when compared with i.v. Genetaxyl, when calculated either on the basis of data for total paclitaxel (30.1%) or unbound paclitaxel (30.6%).

Reduced maintenance of complete protection from emesis for women during chemotherapy cycles.

Women have a significantly higher rate of chemotherapy-induced emesis. We observed that gender was the important predict factor for reducing the maintenance of complete protection from emesis during chemotherapy cycles. Four hundred patients were enrolled in one of two arms in a crossover fashion. Arm A: three 8-mg doses of ondansetron were given intravenously at 4-hour intervals plus dexamethasone 20 mg intravenously from the start of chemotherapy, followed by dexamethasone 5 mg intravenously every 12 hours. Arm B: as in arm A but with three 8-mg doses of ondansetron intravenously given at 24-hour intervals substituted for ondansetron intravenously given at 4-hour intervals. Rates for complete protection from vomiting/nausea through days 1 to 6 were 69.7%/58.4% for Arm A, and 71.2%/60.9% for Arm B, and 69.0%/60.0% for the first chemotherapy cycle. Risk factors for vomiting and nausea included gender and cisplatin dosage. Complete control of vomiting/nausea for patients without emesis during previous cycle(s) was maintained at 91.4%/86.6%, 91.1%/85.2%, 93.9%/89.9%, 94.7%/92.6%, and 94.9%/94.9% during the second through sixth cycles of chemotherapy, respectively. Complete protection from vomiting and nausea was significantly reduced for female patients (p = 0.048 and p = 0.0004, during the second cycle, and p = 0.0006 and p = 0.0008, during the third through sixth cycles, respectively). The results suggest that women had less maintenance for complete protection from both vomiting and nausea during chemotherapy cycles.

Characteristics of patients with hematologic malignancies who received palliative care consultation services in a medical center.

This study aimed to compare the characteristics of patients with hematologic malignancies and solid cancers who received palliative care. A total of 124 patients with hematologic malignancy and 3032 patients with solid cancer, who received palliative care consultation services between 2006 and 2010 in a medical center in Taiwan, were retrospectively analyzed. Higher prevalence of oral stomatitis, diarrhea, and hematologic symptoms including infection, fever, severe anemia, and bleeding, and lower prevalence of constipation, abdominal distension, and pain were observed in patients with hematologic malignancies compared to that in patients with solid cancer. The interval from hospital admission to palliative care referral was longer for patients with hematologic malignancy than that for patients with solid cancer. Hematologists should refer patients earlier, and palliative care specialists should understand the specific needs of patients with hematologic malignancy.

Weekly 24-h infusion of high-dose 5-flurouracil and leucovorin in patients with advanced gastric cancer.

The effect of biochemical modulation of weekly high-dose 5-fluorouracil (5-FU) 24 h infusion by leucovorin (LV) in the treatment of 39 consecutive patients with advanced gastric cancer without prior chemotherapy from October 1996 to August 1997 was examined. There were 21 male and 18 female patients with a median age of 56 years. The regimen consisted of 5-FU 2600 mg/m2 and LV 150 mg administered by 24 h infusion weekly for 6 weeks followed by a 2 week break. The treatment was repeated every 8 weeks until disease progression, patient refusal or unacceptable toxicity. Placement of a central vascular device and a portable external infusion pump was required in all patients and was used for outpatient treatment. The response to treatment was evaluated every 8 weeks. A total of 395 chemotherapy treatments were given with a mean of 10 (2-24). This response rate was: 33% (12 of 36) partial response (PR) rate, 33% (12 of 36) stable disease (SD) and 33% (12 of 36) progressive disease (PD). In general, the toxicity was mild but two toxic deaths occurred, one due to neutropenic sepsis and the other due to hyperammonemia. The median time to progression was 4 months. The overall median survival was 7 months. The survivals of the PR, SD and PD were 12, 8 and 5 months, respectively. This regimen showed a modest activity against gastric cancer with acceptable toxicity. Weekly 24 h infusion of high-dose 5-FU with LV in an outpatient setting for patients with gastric cancer is feasible and deserves further study as a basis for combination therapy.

Cisplatin, tegafur-uracil and leucovorin plus mitomycin C: an acceptably effective and toxic regimen for patients with recurrent or metastatic nasopharyngeal carcinoma.

BACKGROUND This prospective phase II clinical trial evaluated the efficacy and toxicity of cisplatin, oral tegafur-uracil, leucovorin, and mitomycin C in patients with recurrent or metastatic nasopharyngeal carcinoma. METHODS Patients with histologically proven non-keratinizing or undifferentiated nasopharyngeal carcinoma were prospectively enrolled from April 2002 to June 2005. Cisplatin 50 mg/m(2) on day 1, 22 and mitomycin C 6 mg/m(2) on day 1 were administered. Oral tegafur-uracil 300 mg/m(2)/day and oral leucovorin 60 mg/day were given on day 1-14 and day 22-35, respectively. Each cycle was repeated every 6 weeks. Primary and secondary endpoints are response rate and toxic profiles with survivals, respectively. RESULTS Twenty-two patients with the median age of 47 (35-69) years were enrolled in the study. Sixteen (72.7%) patients had undifferentiated nasopharyngeal carcinoma. The regimen was well-tolerated by all patients with the exception of one patient (4.6%) who experienced grade IV anorexia, and two patients (9.1%) who had grade IV vomiting. There was no treatment-related death. The overall response rate was 59.1%, including 3 (13.6%) complete remissions. The median duration of response was 15.9 months, the median time to tumor progression was 10.0 months, and the median overall survival was 16.0 months. CONCLUSION This outpatient chemotherapy regimen is acceptably effective and toxic among patients with recurrent or metastatic nasopharyngeal carcinoma.

Phase I dose escalation study of oxaliplatin combined with oral tegafur-uracil and leucovorin in patients with advanced gastric cancer.

Our aim was to determine the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended dose of oxaliplatin combined with oral tegafur–uracil and leucovorin. Twenty-eight chemo-naïve patients with advanced gastric cancer were enrolled. Oxaliplatin (55, 70, 85, 100 and 115 mg/m2) was given as a 2-h infusion on days 1 and 15. Oral tegafur–uracil (300 mg/m2 per day) and leucovorin (60 mg/day) were given 3 times a day from days 1 to 21 (28-day cycle). DLTs were defined as grade IV hematologic toxicity or grade III non-hematologic toxicity. The MTD for oxaliplatin was 100 mg/m2. The most common DLT was diarrhea. Major grade III/IV toxicities included vomiting, diarrhea, renal dysfunction, leukopenia and thrombocytopenia. There were two treatment-related deaths. Intent-to-treat response was graded as partial response in 13 patients (46.4%; 95% confidence interval 26.74–66.12%), stable disease in nine and disease progression in five. As of June 2004, 17 patients had died. The median time to treatment failure, time to progression and overall survival were 124, 308 and 434 days, respectively. The recommended dose for the phase II study is oxaliplatin 100 mg/m2 biweekly with oral tegafur–uracil (300 mg/m2 per day) and leucovorin (60 mg/day) 3 times a day for 21 days.

INTRA-ABDOMINAL DESMOPLASTIC SMALL CELL TUMORS : REPORT OF TWO CASES

Two young adults that presented with intra-abdominal desmoplastic small cell tumors (DSCT) without any evidence of a primary site are described. Both cases share the clinical characteristic features of this rare tumor which include predominant intra-abdominal location as initial presentation, nesting pattern of growth, intense desmoplastic reaction, immunohistochemical reactivity for epithelial, neural and muscle markers, and highly aggressive behavior. Aggressive chemotherapy with a cisplatin-containing regimen was the main therapy to our patients. Up to the present, both cases are alive with disease. The survival is 18 and 15 months from the initial diagnosis, respectively. Interestingly, one of the cases encountered an episode of cerebral infarction at the territory of the left middle cerebral artery 12 days after the first cycle of chemotherapy. This is a previously unrecognized manifestation for this tumor type. This causal relationship between chemotherapy and an acute vascular event is the most likely explanation for our patients stroke.

Clinical Outcomes of Patients with Resected Oral Cavity Cancer and Simultaneous Second Primary Malignancies.

Objectives Simultaneous second primary tumors (SSPT) are not uncommon in patients with oral cavity squamous cell carcinoma (OSCC) living in areas where the habit of betel quid chewing is widespread. We sought to identify the main prognostic factors in OSCC patients with SSPT and incorporate them into a risk stratification scheme. Methods A total of 1822 consecutive patients with primary OSCC treated between January 1996 and February 2014 were analyzed for the presence of SSPT. The 18-month and 5-year overall survival (OS) rates served as the main outcome measures. Results Of the 1822 patients, 77 (4%) were found to have SSPT (i.e, two malignancies identified within one month of each other). The 18-month and 5-year OS rates in patients without SSPT and with SSPT were 82% and 69%, and 72% and 53%, respectively (p = 0.0063). Patients with SSPT were further divided into patients with either esophageal cancer or hepatocellular carcinoma (eso-HCC subgroup, n = 8) and other tumors (NO eso-HCC subgroup, n = 69). After multivariate analysis, neck nodal extracapsular spread (ECS, n = 18) and the presence of eso-HCC were identified as independent adverse prognostic factors. The 18-month OS rates of SSPT patients with both eso-HCC and ECS (n = 5) vs. the remaining patients (n = 72) were 0% and 78%, respectively (p < 0.0001). Conclusion OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis.