Phase II trial of high-dose continuous infusion 5-fluorouracil with allopurinol modulation in colon cancer

Twenty patients with metastatic colon cancer without prior chemotherapy received 2 g/m2 of 5-fluorouracil (5-FU) infused over 24 h for 5 days preceded by allopurinol 900 mg orally for 1 week and then continued during, and for 1 week after the infusion was completed. Fourteen patients were evaluable for both response and toxicity. One patient (14%) achieved a partial response lasting 2 months. No significant hematologic toxicity was seen but 18 of 19 patients evaluable for toxicity developed mucositis resulting in dose reductions in 3 patients and refusal of a second course by 2 additional patients. 5-FU infusions with allopurinol as used in this regimen appear to offer no therapeutic advantage over a conventional dosing schedule.     

Phase II trial of vinorelbine,cisplatin and continuous infusion of 5-fluorouracil followed by hyperfractionated radiotherapy in locally advanced head and neck cancer

OBJECTIVE: We undertook a prospective phase II study to assess the feasibility and activity of a new induction chemotherapy regimen followed by hyperfractionated irradiation in locally advanced squamous cell head and neck cancer. METHODS: 25 patients with locally advanced head and neck cancer were treated with 4 cycles of vinorelbine (20 mg i.v. day 1, 3), cisplatin (60 mg/m(2) i.v. day 1) and 5-fluorouracil (200 mg/m(2) continuous i.v. infusion day 1-21) (ViFuP regimen) followed by bifractionated radiotherapy (bidRT) up to 74.4 Gy in 62 fractions of 1.2 Gy twice daily. RESULTS: Chemotherapy was well tolerated, 6 patients developed grade 3 and one patient grade 4 neutropenia. Response to chemotherapy was observed in 19 patients (76%) including three complete responses and 16 partial responses. Planned bidRT was completed in 25 patients and all but one received planned bidRT dose without interruptions. Radiotherapy was well tolerated, mucositis was the most common side effect (grade 3-12 patients, grade 4-1 patient). At evaluation after the completion of bidRT, 13 patients had complete response (52%), 7 partial response (28%), 2 stable disease and 3 tumor progression. At the median follow-up of 18.2 months, 11 patients were alive and free of disease, and 14 patients had died (12 of tumor). Late xerostomy was observed in all but one 3-month survivors. Late mandibular necrosis was seen in 1 patient. CONCLUSIONS: bidRT preceded by ViFuP seems a feasible and active combination in locally advanced head and neck cancer. Good patient compliance did not compromise the delivery of planned dose of bidRT. However, short median duration of response (14.6 months) and moderate median overall survival (18.7 months) indicate the need for more intensive therapeutic strategies. On the basis of these results, modifications of our treatment schedule (shortening the overall treatment time by reduction of chemotherapy cycles and the use of chemotherapy concomitantly with irradiation) are planned for the future study.     

Phase II study of carboplatin and continuous infusion bleomycin followed by cisplatin and 5-fluorouracil in recurrent head and neck cancer

BACKGROUND: Recurrent squamous cell carcinoma of the head and neck is poorlyresponsive to most chemotherapy regimens. Carboplatin and bleomycinare effective single agents with non-overlapping toxicity; therefore,we sought to explore the efficacy of this regimen in a phaseII study. In the second stage of the study, patients who didnot respond to carboplatin and bleomycin were given treatmentwith cisplatin and 5-fluorouracil (5-FU). PATIENTS AND METHODS: Patients with recurrent squamous cell carcinoma of the headand neck were treated with carboplatin 400 mg/m² followed bybleomycin 15 units intravenously as a continuous infusion for4 days. Patients with no tumor response after 3 cycles of carboplatinand bleomycin were crossed-over to receive cisplatin 100 mg/m²and 5-FU 1000 mg/m²/day continuous infusion for 5 days. RESULTS: Among the 20 carboplatin-bleomycin patients evaluable for toxicity,no cases of grade 4 granulocytopenia were reported and grade3 or 4 thrombocytopenia developed in only three patients. Threepartial responses occurred among the 19 patients (16%) [95%Cl. 0% to 32% evaluable for response to carboplatin-bleomycin.None of the 11 patients crossed-over to cisplatin and 5-FU hada major response. CONCLUSION: The combination of carboplatin and bleomycin is well toleratedin patients with recurrent head and neck cancer, but the activitydoes not appear to be superior to the activity of either agentalone. Patients who did not respond to carboplatin and bleomycinwere also resistant to the cisplatin and 5-FU regimen. head and neck cancer, chemotherapy     

Phase II study of continuous venous infusion of 5-fluorouracil in advanced pancreatic cancer

Continuous venous infusion of 5-fluorouracil (5FU) was investigated in 18 patients with measureable advanced cancer of the pancreas. 5FU was given for 7 days in a dose of 500 mg/m2 by continuous venous infusion over a 24-hour period and then followed by a dose of 170 mg/m2 for more than 28 days. Ten patients had no change including 1 patient with minor response, and 4 patients had disease progression. Serum CA19-9 levels were measured serially after chemotherapy in 13 of 14 evaluable patients. In 3 of 10 patients who showed high levels before treatment, serum CA19-9 levels were significantly decreasing after treatment.     

Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer

RATIONALE: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. METHODS AND MATERIALS: Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m(2)) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). RESULTS: Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per fraction), improvements were seen in SP (79% vs. 59%; p = 0.02), SP for tumors <6 cm from the anal verge (75% vs. 42%; p = 0.003), and down-staging (86% vs. 62%; p = 0.003). CONCLUSION: The SP rate with concomitant boost radiation has been highly favorable with rates of response which are higher than those previously reported for chemoradiation without administration of a boost. Further evaluation of this radiotherapeutic strategy appears warranted.     

Paclitaxel, carboplatin, and long-term continuous infusion of 5-fluorouracil in the treatment of advanced squamous and other selected carcinomas: results of a Phase II trial

BACKGROUND: The purpose of this study was to evaluate the feasibility, toxicity, and efficacy of the combination of paclitaxel, carboplatin, and long-term continuous infusion 5-fluorouracil (5-FU) in the treatment of advanced squamous carcinomas of various primary sites. METHODS: Patients were eligible for this trial if they had metastatic squamous carcinoma at any site except the lung. In addition, patients with locally advanced squamous carcinoma of the head and neck were eligible, if they were considered unlikely to be cured with combined modality therapy. Sixty patients entered this trial between February 1995 and March 1999; 12 patients (20%) had received 1 previous chemotherapy regimen, whereas 48 patients (80%) were previously untreated. All patients received the following regimen: paclitaxel 200 mg/m(2), 1-hour intravenous infusion, Days 1 and 22; carboplatin area under the concentration-time curve (AUC) 6.0 intravenously, Days 1 and 22; 5-FU 225 mg/m(2)/day, by 24-hour continuous intravenous infusion, Days 1-35. Treatment courses were repeated at 6-week intervals; responding patients continued treatment for a maximum of 4 courses (24 weeks). RESULTS: Thirty-nine of 60 patients treated (65%) had objective responses to this regimen, with 25% complete responses. Twelve patients (22%) remain progression free from 7 to 63 months (median, 35 months) after completion of therapy. Complete responses were observed in squamous carcinomas from various primary sites including head and neck, esophagus, cervix, vagina, anus, and unknown primary. The most frequent Grade 3/4 toxicities observed with this 3-drug regimen included leukopenia (48%), diarrhea (17%), mucositis (28%), and portacath-related events (13%). CONCLUSIONS: The combination of paclitaxel, carboplatin, and long-term infusional 5-FU is feasible, well tolerated, and highly efficacious in patients with advanced squamous carcinomas of various primary sites. This regimen merits further investigation.     

Phase II trial of cyclophosphamide, leucovorin, 5-fluorouracil 24-hour infusion and tamoxifen in pancreatic cancer

Leucovorin modulates the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. 24-hour infusion of 5-FU has been shown to enhance antitumor activity in colorectal cancer compared to bolus infusion. According to experimental data cyclophosphamide and tamoxifen may enhance the effectiveness of leucovorin and 5-FU. A phase II trial was initiated to evaluate the effect of a combination of low-dose cyclophosphamide (C), leucovorin (L), 5-FU (F) and tamoxifen (T) (CLFT) in advanced pancreatic cancer. Fifty patients were treated monthly with 300 mg/m2 cyclophosphamide and weekly with 500 mg/m2 leucovorin followed by a 24-hour infusion of 2000 mg/m2 5-FU and tamoxifen 20 mg bid. Three patients had a partial response (6%), two a minor response (4%) and 32 (64%) no change of disease. The median survival time was 8.5 months for all patients, the median time to progression of disease was 4.6 months and the 1-year survival rate was 28%. CLFT was fairly well tolerated. These data suggest that biochemical modulation of 24-hour infusional 5-FU with leucovorin together with cyclophosphamide and tamoxifen has some positive effects in the treatment of pancreatic cancer.     

Chemoradiation therapy using radiotherapy, systemic chemotherapy with 5-fluorouracil and nedaplatin, and intra-arterial infusion using carboplatin for locally advanced head and neck cancer - Phase II study

To improve the treatment results for locally advanced head and neck cancer, chemoradiation therapy by radiotherapy, systemic chemotherapy with 5-fluorouracil (5FU) and nedaplatin (NDP), and intra-arterial therapy using carboplatin (CBDCA) was performed. Thirty-two patients were entered into the study between July 1997 and August 2002. According to the TNM staging (1997), 14 patients had stage III lesions, and 19 patients had stage IV (M0) lesions. Alternating chemoradiotherapy was performed by the following regimen. Initially, systemic chemotherapy was administered, followed by 4 weeks of radiotherapy (36 Gy/20 fractions; wide field irradiation) starting 2 days after chemotherapy, a second course of systemic chemotherapy 2 days after radiotherapy, and a second course of a reduced field radiotherapy (30 Gy/15 fractions) 2 days after chemotherapy. Arterial injection therapy was administered in the latter half of radiotherapy after the end of the second course of systemic chemotherapy. For systemic chemotherapy, 5FU at 3500 mg/m²/120 h was intravenously administered for 5 days (Days 1–5), and NDP at 120 mg/m²/6 h was administered on Day 6. An intra-arterial agent using CBDCA was continuously infused by a portable electrical pump for 4 (to 6) weeks. The total dose of CBDCA was AUC 6 as established by Calvert’s formula. The 5-year local control rate was 59%. The 5-year overall survival rate was 51%. There were no clinically significant adverse effects. Chemoradiation therapy by radiotherapy, systemic chemotherapy, and intra-arterial chemotherapy for locally advanced head and neck cancer may be useful for improving treatment results.     

Phase II trial of 7-day continuous 5-fluorouracil infusion in the treatment of advanced colorectal carcinoma.

Thirty-eight patients with advanced colorectal adenocarcinoma were entered on a phase II trial of 5-fluorouracil (5-FU) in continuous infusion, using a portable pump. Half of the patients had been pretreated (n = 19) and 16 of them had received intravenous bolus 5-FU alone or in combination. At the first cycle patients received continuous intravenous 5-FU at the dose of 650 mg/m2 per day for 7 consecutive days. Doses were escalated during the following cycles and adjusted according to the toxicities encountered in the previous cycle. Treatment was repeated every 3 weeks. A mean dose of 750 mg/m2/day (500-1,000) was administered for a mean number of 10 (1-25) cycles. We observed 1 complete response, 7 partial responses for a response rate of 21 +/- 13% (CI95%), 16 had stable disease (42%) and 14 a progression (37%). In 2 patients subsequently the residual tumors could be excised after chemotherapy. Median survival was 13.5 months. Toxicity was: grade 2 leukopenia in 1 patient (3%), mucositis grade 2-4 in 11 patients (29%), diarrhea grade 2-3 in 7 patients (18%), and hand and foot syndrome in 12 patients (31%). There was a correlation between the mean dose administered and the responses. However no clear correlation was found between toxicity and tumoral response for the first two cycles. These results confirm the limited efficacy of continuous intravenous 5-FU and its good tolerance in ambulatory patients.     

Phase I trial of 5-fluorouracil and dipyridamole administered by seventy-two-hour concurrent continuous infusion

Forty-seven patients with advanced malignancies were treated with a concurrent 72-h continuous infusion of 5-fluorouracil (FUra) and dipyridamole. The FUra dose was escalated over the dose range of 185 to 3600 mg/m2/day for 3 days. Dipyridamole was administered in a fixed dose of 7.7 mg/kg/day for 3 days. A total of 155 courses of therapy were completed of which there were 31 paired courses of the combination and FUra alone, at the same dose of FUra and in the same patient. This was for purposes of analysis of pharmacokinetics and modulation of FUra toxicity by dipyridamole. Stomatitis was the dose-limiting toxicity experienced by patients entered into this trial. Myelosuppression was not a serious problem. Increasing FUra plasma concentration was associated with greater leukopenia and stomatitis. Dipyridamole did not appear to modulate the systemic toxicity of FUra. The pharmacokinetics of FUra were altered by the concurrent administration of dipyridamole. Dipyridamole promoted the total body clearance of FUra which resulted in lower mean steady-state FUra plasma concentrations when compared with courses of FUra alone administered at the same dose level. These differences were statistically significant over the course of the trial. For courses of the combination, FUra exhibited linear pharmacokinetics over the dose range studied. Total body clearance of FUra declined slightly at the higher dose levels, but the differences were not significant. For courses of FUra alone, total body clearance was significantly decreased above the dose level of 2300 mg/m2/day. At the maximal tolerated dose of FUra, 2300 mg/m2/day x3, mean steady-state FUra plasma concentration and total body clearance were 6.6 microM and 122 liters/h/m2, respectively, for courses of the combination. The corresponding pharmacokinetic parameters were 7.4 microM and 103 liters/h/m2 for courses when FUra was given alone. Further evaluation of the utility of this regimen and basis of these pharmacokinetic observations appear warranted.     

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a Phase II trial for the Trans-Tasman Radiation Oncology Group.

PURPOSE: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. METHODS AND MATERIALS: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. RESULTS: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. CONCLUSION: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications.     

A phase II trial of continuous infusion of 5-fluorouracil, mitoxantrone, and cisplatin for metastatic hepatocellular carcinoma

BACKGROUND: The aim of the current study was to evaluate the antitumor activity and toxicity of continuous infusion of 5-fluorouracil, mitoxantrone, and cisplatin (FMP therapy) in chemotherapy-naive patients with metastatic hepatocellular carcinoma (HCC). METHODS: Fifty-one patients with metastatic HCC who had not undergone previous systemic chemotherapy were enrolled. The therapy consisted of intravenous administration of 80 mg/m2 cisplatin and 6 mg/m2 mitoxantrone on Day 1 and continuous intravenous infusion of 450 mg/m2 5-fluorouracil per day on Days 1-5. The treatment was repeated every 4 weeks for a maximum of 6 courses with dose adjustments based on the observed toxic effects if there was no evidence of tumor progression or unacceptable toxicity. RESULTS: Of the 51 enrolled patients, 14 (27%) achieved a partial response (95% confidence interval, 16-42%) with a median duration of 7.6 months (range, 2.3-18.4 months). Twenty-seven patients (53%) showed no change and 9 (18%) had progressive disease. The median survival time, 1-year survival rate, and median progression-free survival time for all patients were 11.6 months, 44.3%, and 4.0 months, respectively. The main Grade 3 and 4 toxicities were leukocytopenia (67%), neutropenia (71%), thrombocytopenia (27%), and elevated levels of aspartate aminotransferase (37%) and alanine aminotransferase (41%). These symptoms were generally brief and reversible, with the exception of one treatment-related death due to acute hepatic failure. CONCLUSIONS: FMP therapy had significant antitumor activity with acceptable toxicity in patients with metastatic HCC.     

Phase II trial of preoperative 3D conformal radiotherapy,protracted venous infusion 5-fluorouracil,and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer

PURPOSE: CPT-11 sensitizes tumor cells to radiation and in combination therapy with 5-fluorouracil (5-FU) results in enhanced cytotoxicity to metastatic colorectal cancer. We report the results from a Phase II trial of preoperative radiotherapy (RT), CPT-11, and 5-FU for patients with ultrasound-staged T3 rectal cancer. METHODS AND MATERIALS: Between April 1999 and August 2001, 32 patients (21 men, 11 women; median age 52 years, range 40-74) with biopsy-proven adenocarcinoma of the rectum were enrolled in the study. All patients underwent endorectal ultrasonography for staging (uT3N0 = 19; uT3N1 = 13; uT2N1 = 1). RT was prescribed to the draining lymph nodes (45 Gy in 1.8-Gy daily fractions) and tumor (50.4 Gy in 1.8-Gy daily fractions). Patients also received concurrent CPT-11 (50 mg/m(2), Days 1, 8, 15, and 22) and 5-FU (200 mg/m(2) daily, 7 d/wk, Days 1-33). Surgical resection was performed 6-10 weeks after completing chemoradiotherapy. RESULTS: Acute toxicity was frequently observed, and 18 patients (56%) required either a chemotherapy dose reduction or RT interruption of >3 days. One patient withdrew because of diarrhea and abdominal cramping (Grade III) after 10 days of treatment. Although no Grade IV toxicity was observed, Grade III diarrhea (n = 9, 28%), mucositis (n = 7, 21%), rectal sores (n = 7, 21%), abdominal cramping (n = 3, 9%) were noted. Of the 32 patients who underwent surgery, 12 had a complete pathologic response. Of the 32 patients, the disease of 23 (71%) was downstaged. The average length of hospitalization was between 5 and 12 days, with 1 patient staying 33 days. All patients were followed for disease-free survival. CONCLUSION: Although associated with frequent acute toxicity, the regimen is associated with significant tumor "downstaging." Additional patients and longer follow-up are necessary to define the role of this regimen fully.     

Low-dose continuous intravenous infusion of 5-fluorouracil for metastatic breast cancer

BACKGROUND:: Third-line chemotherapies for advanced breast cancer are difficultto tailor to the individual patient because of reduced toleranceand significant toxicity. Treatment with a continuous intravenousinfusion of low-dose 5-fluorouracil (FU-LDCI) is generally welltolerated and thus, a reasonable option for heavily pretreatedpatients. PATIENTS AND METHODS:: From 1989 to 1995,106 consecutive patients with advanced breastcancer were treated with FU-LDCI. 5-Fluorouracil was given atan initial daily dose of 250 mg/m² administered continuouslywith the aid of an elastomer, non-electronic pump through apermanent central venous line for 21 days followed by a 7-dayrest. The median age was 56 years (range, 30–82), themedian ECOG Performance Status was 1 (range 0–4) and themedian number of metastatic sites was 2 (range 1–4). Sixty-onepercent of the patients had previously received more than 2chemotherapy regimens which in 81% included adriamycin, andin 90% 5-fluorouracil. RESULTS:: Eighty patients were evaluable for objective response: 17 ofthem had partial responses (21%, 95% CI: 14%–31%) and23 stable disease (29%, 95% CI: 20%–40%). One-hundredfive patients were evaluable for subjective response, with 46reporting improvement (44%,95% CI: 35%–54%). Previoustreatments with either 5-fluorouracil or adriamycin did notpredict response to FU-LDCI. Median time to progression forpatients with a partial response or stable disease was 259 days(range 82–737). The overall survival for the populationsas a whole was 274 days (range 13–2264), and the mediandose received was 1904 mg/week (range 753–4329). The maintoxic effects were grades I and II mucositis, and nausea andvomiting (observed in 31% and 28%, respectively). Grade IIItoxicities were uncommon: mucositis in 3%, nausea and vomitingin 3%, anemia, thrombocytopenia and hepatitis in 2%, and skintoxicity (hand-foot syndrome) in 1%. Catheter-related thrombosiswas observed in 2% of the patients, and there were no pump failures.A questionnaire concerning the impact of the treatment uponquality of life was completed by all of the 13 patients whowere alive at the time of evaluation of the results, and allof them rated FU-LDCI as easy to tolerate. The monthly costof FU-LDCI (USS1,051.00 in Switzerland) was lower than the costof weekly low-dose adriamycin (USS1,483.00 in Switzerland),a treatment which is often used as a palliative regimen in similarcircumstances. CONCLUSIONS:: FU-LDCI is a useful, cost-effective third-line treatment forpatients with metastatic breast cancer who need palliation withcytotoxic drugs. advanced breast cancer, chemotherapy, 5-fluorouracil infusion, financial costs, low-dose continuous, palliative therapy, quality of life     

Phase II trial of combination chemotherapy for pancreatic cancer with 5-fluorouracil, mitomycin C, and hexamethylmelamine

A combination consisting of hexamethylmelamine 150 mg/m2 D2-15, mitomycin C 10 mg/m2 D2 and 5-fluorouracil 30 mg/kg/day as a continuous infusion for 5 days, in 4-5 week cycles, underwent phase II trial as primary therapy for 21 patients with regional and metastatic cancer of the pancreas. Median survival from the onset of therapy was 43 weeks. There were 2 complete responses, 4 minor responses and 6 stable diseases for more than 6 months. Nonambulatory patients were among the responders. There was only 1 life-threatening toxicity (thrombocytopenia) and only 33% of patients had clinically silent severe hematological toxicity. The regimen is well tolerated, active and associated with excellent survival. This regimen is suitable for further confirmatory trials.     

Carboplatin and continuous infusion 5-fluorouracil for advanced head and neck cancer

Fifty-one patients with recurrent or advanced squamous cell carcinoma of the head and neck received carboplatin 70 mg/m²/day bolus × 5 days i.v. and 5-fluorouracil (5-FU) 1000 mg/m²/day by continuous infusion i.v. for 5 days as initial chemotherapy. There were four complete responders (CR) and 12 partial responders (PR). Durations of CR were 6.8 months, 7.2+ months and 14.8+ months with one patient lost to follow up after achieving CR. For objective responders the median relapse-free survival from the time of response was 5.3 months and survival from registration 11.7 months. The median survival for all patients was 4.8 months. The major toxicities were myelosuppression and mucositis. Neutropenia (<1.0 × 10⁹/l) occurred in 19% of patients, thrombocytopenia (<50 × 10⁹/l) in 17% and severe (WHO grade three or four) mucositis was experienced by 28% patients. This combination had less gastrointestinal and nephrotoxicity than platinum containing combinations and can be used in patients with a poorer performance status.     

Phase II trial of sorafenib in combination with 5-fluorouracil infusion in advanced hepatocellular carcinoma

Abstract  

     

Phase II trial of hypofractionated image-guided intensity-modulated radiotherapy for localized prostate adenocarcinoma

PURPOSE: To assess in a prospective trial the feasibility and late toxicity of hypofractionated radiotherapy (RT) for prostate cancer. METHODS AND MATERIALS: Eligible patients had clinical stage T1c-2cNXM0 disease. They received 60 Gy in 20 fractions over 4 weeks with intensity-modulated radiotherapy including daily on-line image guidance with intraprostatic fiducial markers. RESULTS: Between June 2001 and March 2004, 92 patients were treated with hypofractionated RT. The cohort had a median prostate-specific antigen value of 7.06 ng/mL. The majority had Gleason grade 5-6 (38%) or 7 (59%) disease, and 82 patients had T1c-T2a clinical staging. Overall, 29 patients had low-risk, 56 intermediate-risk, and 7 high-risk disease. Severe acute toxicity (Grade 3-4) was rare, occurring in only 1 patient. Median follow-up was 38 months. According to the Phoenix definition for biochemical failure, the rate of biochemical control at 14 months was 97%. According to the previous American Society for Therapeutic Radiology and Oncology definition, biochemical control at 3 years was 76%. The incidence of late toxicity was low, with no severe (Grade > or =3) toxicity at the most recent assessment. CONCLUSIONS: Hypofractionated RT using 60 Gy in 20 fractions over 4 weeks with image guidance is feasible and is associated with low rates of late bladder and rectal toxicity. At early follow-up, biochemical outcome is comparable to that reported for conventionally fractionated controls. The findings are being tested in an ongoing, multicenter, Phase III trial.     

Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer: preliminary results of a Minnie Pearl Cancer Research Network phase II trial

PURPOSE: To evaluate the feasibility, toxicity, and therapeutic efficacy of 1-hour paclitaxel, carboplatin, continuous low-dose infusional 5-fluorouracil, and concurrent radiation therapy administered preoperatively in patients with localized esophageal cancer. PATIENT AND METHODS: Forty-nine patients with localized esophageal cancer, of either squamous cell carcinoma or adenocarcinoma histology, were enrolled into this phase II trial. All patients were candidates for surgical resection and received the following neoadjuvant therapy: paclitaxel, 200 mg/m2, 1 hour IV on days 1 and 22; carboplatin, AUC 6.0, IV on days 1 and 22; 5-fluorouracil, 225 mg/m2/day, continuous IV infusion on days 1 to 42; and radiation therapy, 45 Gy, administered by 1.8-Gy daily fractions beginning on day 1 of chemotherapy. Upon completion of this neoadjuvant regimen, patients were reevaluated, and all responding patients were resected within 6 weeks of completing neoadjuvant treatment. RESULTS: Administration of this combined modality regimen was associated with moderate toxicity and was tolerated by most patients. Leukopenia (65%) and esophagitis (31%) were the most common toxicities. Most patients did not require nutritional support. There were no treatment-related deaths during neoadjuvant therapy; however, three patients (9%) experienced postoperative death. Preliminary assessment of treatment efficacy is encouraging, with 17 of 37 evaluable patients (46%) achieving pathologic complete remission and an additional 11 patients (30%) having only microscopic residual disease. CONCLUSIONS: This novel, combined-modality neoadjuvant approach for the treatment of localized esophageal carcinoma is feasible and can be administered with toxicity that compares favorably to previously reported neoadjuvant regimens containing high-dose cisplatin. Preliminary assessment of efficacy is also encouraging, with 46% of patients having pathologic complete response. Further follow-up and larger numbers of patients are required to assess efficacy more definitively.