Prospective randomised phase II study of gemcitabine at standard or fixed dose rate schedule in unresectable hepatocellular carcinoma.

The present randomised phase II study was an effort to evaluate single-agent gemcitabine as a first-line systemic treatment of Asian patients with unresectable hepatocellular carcinoma (HCC). Gemcitabine was given via intravenous infusion at 1250 mg m(-2) on days 1 and 8 of 3-week cycles. Patients were randomised to receive gemcitabine as a 30-min intravenous infusion (standard schedule) or at a fixed dose rate (FDR) of 10 mg m(-2) min(-1). A total of 50 patients were enrolled in the study, of whom 48 received study therapy. One patient on standard schedule had a partial response, for an overall response rate of 2.1% (95% CI: 0.05-11.1%). The median time to progression and survival time were 46 and 97 days, respectively. The overall rates of Grade 3 or 4 haematological and nonhaematological toxicities were 39.6 and 64.6%, respectively, with no significant difference between the two treatment arms. There were no drug-related deaths and severe clinical toxicities were rare. Both schedules of gemcitabine were safe and toxicity was well manageable in this patient population. However, gemcitabine seems no more active than other cytotoxic agents when used alone for systemic treatment of advanced HCC.

Phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer.

We conducted a phase II trial to investigate the efficacy of concurrent chemoradiation in patients with stage III non-small-cell lung cancer (NSCLC). Thirty patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Patients received six weekly cycles of paclitaxel 45 mg/m(2) over 1 h; carboplatin at (area under the curve) AUC 2; and radiation therapy of 60 Gy. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy over 4 weeks) followed by a boost to the primary tumor (20 Gy in 2 weeks). After the initial phase of concurrent chemoradiation, patients received an additional four cycles of paclitaxel 175 mg/m(2) over 3 h and carboplatin at AUC 6 every 3 weeks. The overall objective response rate of 30 assessable patients was 76.7%. At the median follow-up time of 13.1 months, the median survival time was 14.5 months (95% CI, 10.59-18.48). The median progression-free survival was 10.5 months (95% CI, 7.72-13.28). The major toxicity was hematologic. The incidence of grade 3 esophagitis was 10%. In conclusion, this chemoradiation regimen is well tolerated and shows significant clinical results for locally advanced NSCLC. Locoregional failure rate remains an important issue with this newer chemotherapeutic regimen. A novel chemotherapy and radiation therapy is clearly needed.

Efficacy of UFT plus oral leucovorin in advanced colorectal cancer: a multicenter study.

PURPOSE: To evaluate the efficacy and toxicity of UFT plus oral leucovorin in advanced colorectal cancer. MATERIAL AND METHOD: Twenty cases of advanced colorectal cancer were entered into the study. All patients must have histologic proof and have measurable disease. Prior to the treatment all patients should have normal baseline hematology and normal liver and renal function, ECOG Performance status < or = 2 and age 18-75 years. Chemotherapeutic drugs consisted of UFT 350 mg/m2/day divided into 3 doses (8 hours apart) plus oral leucovorin 15 mg every 8 hours. Duration of treatment was 21 days per each cycle. Treatment was recycled every 28 days. RESULTS: Four cases (22.2%) had partial responses and six cases (33.3%) had stable disease. Duration of response was 4(+)-7+ months. Toxicity was darkened skin, mild diarrhea and mild alopecia. CONCLUSION: UFT plus oral leucovorin was one of the active regimens in the treatment of advanced colorectal cancer.

Phase II study of concurrent chemoradiotherapy for inoperable (bulky) stage III (A/B) non-small cell lung cancer (NSCLC): a preliminary report.

We designed a phase II study to determine the feasibility and toxicity of concomitant radiotherapy and Paclitaxel/Carboplatin followed by adjuvant chemotherapy of the same regimen in patients with newly diagnosed inoperable stage III A/B non-small cell lung cancer. Patients were irradiated with a total dose of 66 Gy. Weekly courses of Paclitaxel 45 mg/m2 and Carboplatin AUC 2 were administered intravenously during the irradiation period. After completion of concurrent chemoradiotherapy, adjuvant chemotherapy with Paclitaxel 175 mg/m2 and Carboplatin AUC 6 intravenously every 3 weeks for 4 cycles were given. Since March 1998, 15 patients have been enrolled. All patients were assessable for efficacy and toxicity after concurrent chemoradiotherapy. Eleven patients were assessable for efficacy and toxicity after adjuvant chemotherapy. After concomitant chemoradiotherapy, complete response (CR) was documented in 2 of 15 (13%). Partial response (PR) was documented in 9 of 15 (60%). After completion of adjuvant chemotherapy in 11 patients, the overall response rate was 91 per cent. (18% CR, 73% PR). There were 8 per cent gr. 3-4 neutropenia which occurred during adjuvant chemotherapy. Concomitant Paclitaxel/Carboplatin and radiotherapy are promising modalities in the treatment of inoperable stage III A/B non-small cell lung cancer.

Phase II study of paclitaxel and carboplatin for advanced non-small-cell lung cancer.

A prospective phase II study was conducted to determine the response, toxicity and survival rate of lung cancer patients treated with combination paclitaxel and carboplatin in stage IIIB and IV NSCLC. Eligible patients required measurable and/or evaluable diseases; performance status (ECOG) 0-2; no previous chemotherapy; adequate hepatic, renal and bone marrow function. Paclitaxel was administered at a dose of 200 mg/m2, 3 h infusion, followed by carboplatin at an AUC of 6. Treatment was repeated every 3 weeks for six courses. G-CSF 5 microgram/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leucopenia or granulocytopenia in the previous course. From April 1996 through July 1997, 53 patients were enrolled; all are assessable for toxicity and response. The median age was 56 years (range, 20-77 years). Sixty four percent were male, 64% had adenocarcinoma and 62% had stage IV disease. Two hundred and seventy two courses were administered; 36 patients (68%) completed all six cycles. Two patients achieved a complete response (4%) and 27 patients achieved a partial response (51%), for an overall response rate of 55%. Sixteen patients had stable disease (30%) and 8 patients had progressive disease (15%). The median progression free survival time for all patients, stage IIIB and stage IV patients was 28 weeks (range, 18-37 weeks), 31 weeks (range 21-41 weeks) and 22 weeks (range 16-29 weeks), respectively. The median survival time and 1 year survival rate for all patients was 55 weeks (range, 51-59 weeks) and 55%, respectively. Stage IIIB patients had better median survival time and 1-year survival rate than stage IV patients (75 vs. 46 weeks, P = 0.007; 80% vs. 42%, P = 0.003). Grade 3 and 4 granulocytopenia, anemia and thrombocytopenia were observed in 25, 3, and 1%, respectively, of the 272 courses administered. G-CSF was required in 28% of the 272 courses. There were four episodes of febrile neutropenia (1.5%), three episodes of angina pectoris (1%) and one episode of anaphylaxis (0.4%). Other common toxicities, generally mild, included myalgia, arthralgia, peripheral neuropathy and asthenia. Most toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.

Phase II study: concurrent chemo-radiotherapy in advanced nasopharyngeal carcinoma.

This prospective clinical trial was conducted in previously untreated patients with stage IV nasopharyngeal carcinoma (TNM classification), who received concurrent chemo-radiotherapy regimen of cisplatin and radiation, followed by adjuvant chemotherapy consisting of 5FU and cisplatin. The aim was to improve both disease free survival and overall survival. From July 1991 to June 1993, 28 patients with stage IV (T1-4N2-3 M0) squamous cell carcinoma or undifferentiated cell carcinoma of the nasopharynx were treated at the Pramongkutklao Hospital with radical radiotherapy and concurrent chemotherapy using cisplatin 100 mg/m2 on day 1 and 22 of radiotherapy. Adjuvant chemotherapy consisted of cisplatin 100 mg/m2 day 1 and 5FU 800 mg/m2 continuous intravenous infusion 24 hours for day 1-4 and repeated every 4 weeks, for 4 courses. All twenty eight cases had documented stage IV without distant metastases. 11/28 and 16/28 had T4 and N3 disease respectively. The initial response to concurrent chemo-radiotherapy was 100 per cent (27 CR, and 1 PR). With a median follow-up period of 58 months, the 2-year and 4-year survival rates were 85 per cent and 78 per cent respectively. Concurrent chemo-radiotherapy and adjuvant chemotherapy was well tolerated and without significant acute or chronic toxic effect, only a few patients had grade 3 and 4 mucositis and hematologic toxicity. At median time to follow-up of 58 months, seven patients developed loco-regional recurrence and two had distant metastases at the time of analysis. The results of this prospective study demonstrated that concurrent chemo-radiotherapy could induce a durable complete remission in a high proportion of patients with poor-prognosis stage IV nasopharyngeal carcinoma, resulting in an improved overall 2 and 4-year survival when compared to historical control of radiation therapy alone.

Lack of protection against bacterial infections in patients with advanced cancer treated by biologic response modifiers.

A survey of patients with advanced cancer treated by biologic response modifiers (BRMs), including (i) recombinant interleukin-2 and lymphokine-activated killer cells, (ii) recombinant interleukin-2 and alpha interferon, and (iii) tumor necrosis factor, was done. A total of 52 patients were reviewed. A total of 73 courses of BRMs were administered. Prior to the initiation of therapy, all patients were infection free and not receiving antibiotics. Twelve patients developed bacteremia during treatment with these BRMs. Five of these 12 patients had catheter-related bacteremia. Six patients had bacteremic infections without an obvious source, and one patient had a urinary tract infection with bacteremia. Staphylococcus epidermidis accounted for six of the isolates. Other organisms were Staphylococcus aureus, group B streptococci, viridans group streptococci, and gram-negative bacilli. This was an unexpectedly high incidence of bacterial infections in patients treated with BRMs. These BRMs have been previously shown to be efficacious against infections (by bacteria and other intracellular organisms) in experimental animals. In this study BRMs did not influence host defense mechanisms or offer protection against bacterial infections.

Pharmacokinetics of amikacin in hematologic malignancies.

The pharmacokinetics of amikacin in 10 patients with hematologic malignancies and 1 patient with aplastic anemia were investigated. At an administered dose of 7 mg/kg of body weight, a volume of distribution of 0.4 liters/kg, an elimination half-life of 3.0 h, and a total body clearance of 2.1 ml/min per kg, amikacin achieved a peak level in blood of 21 micrograms/ml. Results of the study revealed that there was a marked increase in volume of distribution of amikacin in these patients compared with normal.