Typhlitis in childhood cancer

BACKGROUND: Typhlitis is increasingly recognized in children undergoing chemotherapy but is poorly characterized. The authors investigated the demographic, clinical, and imaging (ultrasonography and computed tomography [CT] scans) variables related to the diagnosis, risk, and outcome of typhlitis. METHODS: The authors reviewed the records of patients who had typhlitis (bowel wall thickness > or = 0.3 cm plus clinical findings) during treatment at St. Jude Children's Research Hospital (Memphis, TN) between 1990 and 2001. They assessed whether duration of typhlitis was related to bowel wall thickness, extent of colonic involvement, ascites, demographics, primary diagnosis, symptoms of typhlitis, or duration of neutropenia. To identify risk factors for typhlitis, the authors compared the demographic data and previous drug therapy of 78 patients who had typhlitis and 1231 identically treated children who did not. RESULTS: Of 3171 children, 83 (2.6%) developed typhlitis. Frequent symptoms were abdominal pain (91%), fever (84%), abdominal tenderness (82%), and diarrhea (72%). Twelve percent of the patients were not neutropenic. Duration of typhlitis was associated with bowel wall thickness measured by ultrasonography (n = 68; P = 0.05) but not CT scan (n = 48; P = 0.67) and was associated with duration of neutropenia (P = 0.02), fever (P = 0.01), and abdominal tenderness (P = 0.04). Age >16 years at cancer diagnosis was the only demographic factor associated with typhlitis (P = 0.03). Two patients died of typhlitis. CONCLUSIONS: Ultrasonography was a useful imaging modality for children with suspected typhlitis. The classic triad of abdominal pain, fever, and neutropenia may be absent. The severity of typhlitis was related to the duration of neutropenia and the presence of fever or abdominal tenderness.     

The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia

The treatment of acute leukemia in childhood has been increasingly successful. Infectious complications are the major cause of morbidity and mortality among these patients receiving aggressive chemotherapy. In particular, neutropenic enterocolitis or typhlitis has had a reported mortality of 50% to 100%. The authors reviewed a series of 77 previously untreated patients with acute myelogenous leukemia begun on treatment from March 1976 to June 1984 to better define the characteristics of typhlitis and its optimum management. Twenty-five patients had episodes of typhlitis, characterized by fever, abdominal pain, and tenderness, occurring during periods of neutropenia. Ten of these patients had watery diarrhea as a major additional symptom, and nine patients had a significant episode of gastrointestinal bleeding. In seven instances, blood culture results were positive, all for intestinal flora. The episodes of typhlitis occurred most frequently during the induction therapy (19 patients). Five patients experienced typhlitis during maintenance therapy, and one patient had acute appendicitis. Two patients had typhlitis during their reinduction therapy, and of note, one had had abdominal symptoms during her initial induction. All patients were treated initially with broad-spectrum antibiotics and bowel rest. Four criteria have been used for surgical intervention: (1) persistent gastrointestinal bleeding after resolution of neutropenia and thrombocytopenia and correction of clotting abnormalities; (2) evidence of free intraperitoneal perforation; (3) clinical deterioration requiring support with vasopressors, or large volumes of fluid, suggesting uncontrolled sepsis; and (4) development of symptoms of an intra-abdominal process, in the absence of neutropenia, which would normally require surgery. Using these criteria, five patients required surgical intervention for typhlitis or its sequelae and one for acute appendicitis. There was one perioperative death resulting from miliary tuberculosis. Among the 21 patients managed medically, there was 1 death resulting from typhlitis in a patient in whom surgery was deferred because of her multiple failures to enter remission.     

Typhlitis. An 18-year experience and postmortem review

A review of pediatric autopsy results at the Texas Children's Hospital, Baylor College of Medicine from 1970 through 1987 was conducted. Thirty-three cases of typhlitis were identified in patients with acute leukemia and two cases each in patients with lymphoblastic lymphoma and aplastic anemia. Patients ranged in age from 10 months to 17 years. Fifty-seven percent were male and 43% were female. All were myelosuppressed. A postmortem incidence rate of 24% was determined for patients with acute leukemia. Common symptoms included abdominal pain and distention in 78% of patients and acute lower gastrointestinal bleeding in 35%. Abdominal radiographs varied in spectrum from a nonspecific bowel gas pattern to frank right colonic pneumatosis intestinalis. Thirty-three patients received chemotherapy within 30 days before onset of abdominal symptoms. All patients were febrile (greater than 38.5 degrees C), and 33 received broad-spectrum antibiotics. Three patients received amphotericin B. Premortem, 84% of organisms cultured from blood were bacterial whereas 16% were fungal. Fungal pathogens accounted for 53% of new microorganisms seen at autopsy. Postmortem examination showed typhlitis in the following anatomic distributions: (1) confined to the cecum; (2) involving the cecum and ileum; (3) involving the cecum, ileum, and ascending colon; or (4) involving the cecum, with sporadic ulcers throughout the intestine. This review includes clinical and postmortem features of typhlitis and current strategies for diagnosis and management.     

Phase I and pharmacologic study of infusional topotecan and Carboplatin in relapsed and refractory acute leukemia.

PURPOSE: To assess the maximum tolerated dose, toxicities, pharmacokinetics, and antileukemic activity of topotecan and carboplatin in adults with recurrent or refractory acute leukemias. EXPERIMENTAL DESIGN: Patients received topotecan and carboplatin by 5-day continuous infusion at nine dose levels. Patients achieving a complete remission received up to two additional courses for consolidation. Plasma topotecan and ultrafilterable platinum were assayed on days 1 to 5. In addition, pretreatment levels of various polypeptides in leukemic cells were examined by immunoblotting to assess possible correlations with response. RESULTS: Fifty-one patients received a total of 69 courses of therapy. Dose-limiting toxicity consisted of grade 4/5 typhlitis and grade 3/4 mucositis after one course of therapy or grade 4 neutropenia and thrombocytopenia lasting >50 days when a second course was administered on day 21. Among 45 evaluable patients, there were 7 complete remissions, 2 partial remissions, 1 incomplete complete remission, and 1 reversion to chronic-phase chronic myelogenous leukemia. Topotecan steady-state plasma concentrations increased with dose. No accumulation of topotecan or ultrafilterable platinum occurred between days 1 and 5 of therapy. Leukemic cell levels of topoisomerase I, checkpoint kinase 1, checkpoint kinase 2, and Mcl-1 correlated with proliferating cell nuclear antigen but not with response. In contrast, low Bcl-2 expression correlated with response (P = 0.014, Mann-Whitney U test). CONCLUSIONS: The maximum tolerated dose was 1.6 mg/m(2)/d topotecan plus 150 mg/m(2)/d carboplatin. The complete remission rate in a heavily pretreated population was 16% (33% at the highest three dose levels). Responses seem to correlate with low pretreatment blast cell Bcl-2 expression.     

Typhlitis in acute leukemia: successful treatment by early surgical intervention.

Inflammation of the cecum ("typhlitis") has been an unusual, but generally fatal complication of severe granulocytopenia and immunosuppression, occurring during the therapy of hematological malignancies. The diagnosis has usually been made only at autopsy, and early surgical intervention has often been withheld because of the patient's precarious hematological status. We report here a patient in whom the clinical diagnosis of typhlitis led to early operation, with intensive blood component support. The successful outcome suggests that such an approach might improve the usually grim prognosis in patients whose underlying malignancy offers a clear chance for remission.     

Risk factors for typhlitis

A case-control study was undertaken to identify risk factors for typhlitis in patients with hematological malignancies. A data base file with a total of 410 episodes of fever and neutropenia in patients cared for between May 1987 and 1996 was reviewed. Typhlitis was defined as a symptom complex of fever, intense abdominal pain and tenderness in the presence of neutropenia. Five cases of typhlitis were identified. Three controls for every patient were randomly selected from the same cohort. Diarrhea and jaundice were more frequent in patients than in controls (p=0.03). The presence of mucositis, prolonged duration of profound neutropenia and idarubicin treatment proved to be risk factors for typhlitis.     

Combined etoposide and 5-azacitidine in children and adolescents with refractory or relapsed acute nonlymphocytic leukemia: a Pediatric Oncology Group Study

An intensive regimen of combined etoposide (VP-16) and 5-azacitidine (5-Az) was used to treat 96 children and adolescents with refractory or relapsed acute nonlymphocytic leukemia (ANLL). Patients were given two sequential five-day courses of VP-16, 250 mg/m2 for three days, followed by 5-Az, 300 mg/m2 for two days. An additional five-day course was administered if marrow aplasia was not evident by day 13. A complete remission rate of 45% was achieved with a median of two courses of VP-16 and 5-Az. The outcome of induction therapy was not influenced by prior treatment, blast cell morphology, or disease status on study entry (refractory or relapsed). Twenty-seven patients have relapsed after remission periods of 35 to 920 days (median, 110 days); seven others are free of leukemia for up to 519 days. The effectiveness of VP-16/5-Az combination therapy in patients refractory to anthracyclines and cytarabine indicates a potential role for these compounds in first-line treatment of patients with ANLL.     

Bolus versus infusion regimens of etoposide and cisplatin in treatment of non-small cell lung cancer: a study of the North Central Cancer Treatment group

In an effort to test clinically the hypothesis that the duration of cellular exposure to etoposide (VP-16) and cisplatin (CDDP) is an important determinant of cytotoxicity, we performed a phase III randomized trial comparing an outpatient bolus regimen of combined VP-16 and CDDP with a sequential infusion over 72 hours of these same two drugs. All patients had stage IV non-small cell lung cancer, and survival was the primary end point. Of 113 patients randomly allocated to the study, 108 were assessable for response, survival, and toxicity. A major response was observed in 20 (37%) of 54 patients on the bolus regimen and in 16 (30%) of 54 patients receiving infusion therapy. The median time to progression was 61 and 88 days for bolus and infusion therapy, respectively. The median survival time was 148 and 157 days, respectively (P = .71). Study results were not consistent with the possibility that infusion therapy could be associated with a 50% improvement in median survival, i.e. from 5 months to 7 1/2 months. Toxicity was primarily myelosuppression and was significantly greater with the infusion regimen. We conclude that infusion therapy as tested in this protocol with VP-16 and CDDP does not offer any advantage in response rate, time to disease progression, or survival as compared with bolus therapy. In addition, infusion therapy is associated with a greater degree of neutropenia and more treatment-related deaths.     

Predictive value of regression rates following chemotherapy of small cell carcinoma of the lung

Tumor volumes measured at the time of initial therapy, during the 28 days following treatment, and following subsequent courses of therapy for 29 patients with small cell carcinoma of the lung were determined from serially measurable roentgenographic lesions. Tumor-halving times were calculated following initial therapy, and the proportions of pretreatment tumor volumes were evaluated within 28 days after initial therapy for 26 patients. Pretreatment tumor volumes ranged from 22.5 to 485 cu cm, with a median of 87 cu cm, a log mean of 83 cu cm, and a linear mean of 113 cu cm. The tumor-halving times ranged from 4 to 86 days, with a median of 12 days, a log mean of 12 days, and a linear mean of 16 days. The reduction of tumor volume expressed as a proportion of pretreatment volume following therapy ranged between 0.02 and 0.65, with a median value of 0.22, a log mean of 0.18, and a linear mean of 0.26. Using the linear mean of 0.26 as a discriminant for survival analysis, patients with less than 0.26 had a median duration of survival of 12 months, which was significantly longer (p = 0.035) than the median survival of 8 months for patients with greater than 0.26. Tumor-halving time of 16 days was also able to separate the survival durations of 12 months of those less than 16 days compared to 8 months for greater than 16 days (p = 0.0429). Tumor regression rate, determined from two consecutive tumor volume measurements, was correlated with the tumor volume (r = 0.677; p less than 0.0001); and volume dependency of the tumor regression rate, as specified in Gompertzian kinetics, was demonstrated.     

Protracted intermittent schedule of topotecan in children with refractory acute leukemia: a pediatric oncology group study.

PURPOSE: To determine dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of a protracted, intermittent schedule of daily 30-minute infusions of topotecan (TPT) for up to 12 consecutive days, every 3 weeks, in children with refractory leukemia. PATIENTS AND METHODS: Forty-nine children were enrolled onto this phase I trial (24 with acute nonlymphoblastic leukemia [ANLL] and 25 with acute lymphoblastic leukemia [ALL]). TPT dosage was escalated from 2.0 to 5.2 mg/m(2)/d for 5 days and 2.4 mg/m(2)/d from 7 days to the same dose for 9 and 12 days in cohorts of three to six patients when no DLT was identified. TPT pharmacokinetics were studied in 33 children once or twice (first and last doses in patients who received TPT for > 7 days). RESULTS: Seventy assessable courses of TPT were administered to 49 children who had refractory leukemia. DLTs were typhlitis, diarrhea, and mucositis, and the MTD was 2.4 mg/m(2)/d for 9 days in this group of heavily pretreated children. In 33 patients, the median TPT lactone clearance after the first dose was 19.2 L/h/m(2) (range, 9.4 to 45.9 L/h/m(2)) and did not change during the course. There were significant responses (one complete response [CR] and four partial responses [PR] in patients with ANLL and one CR and two PRs in patients with ALL), and all but one were at dosages of TPT given for at least 9 days. CONCLUSION: The MTD was 2.4 mg/m(2)/d for 9 days. Further testing is warranted of TPT's schedule dependence in children with leukemia.     

Successful reinduction therapy with amsacrine and cyclocytidine in acute nonlymphoblastic leukemia in children. A report from the Childrens Cancer Study Group.

Amsacrine (AMSA) and cyclocytidine were studied as retrieval therapy in 122 pediatric patients with acute nonlymphoblastic leukemia (ANLL). Patients either failed to achieve sustained initial remissions or were in relapse. Induction therapy consisted of intravenous (IV) AMSA (75 mg/m2) from days 1 to 5 and subcutaneous cyclocytidine (600 mg/m2) from days 1 to 7. Maintenance therapy consisted of IV etoposide (VP-16) (100 mg/m2) for 5 days and IV AMSA (100 mg/m2) on day 1. Of 122 patients, 109 were evaluable. There were 13 early deaths. Ninety-six patients received adequate therapy defined as completion of two courses of therapy. Of these 96 patients, 52 achieved complete remission. Fifteen of 33 patients who failed initial induction achieved complete remission. Eighteen of 39 patients who were resistant to anthracyclines had complete responses. There was no direct evidence of AMSA-induced cardiotoxicity. Remission duration was 28 days to 3 or more years (median, 98 days). AMSA and cyclocytidine were effective retrieval therapy for patients who were in relapse or unresponsive to frontline therapy. Duration of remission was short (median, 98 days).     

Cerebrospinal fluid asparagine concentrations after Escherichia coli asparaginase in children with acute lymphoblastic leukemia.

PURPOSE: The CNS is an important sanctuary site in childhood acute lymphoblastic leukemia (ALL). CSF asparagine concentration reflects asparaginase systemic pharmacodynamics. We evaluated the time course of CSF asparagine depletion in children with ALL during and after a course of Escherichia coli asparaginase. PATIENTS AND METHODS: Thirty-one children (24 newly diagnosed and seven at relapse) received E coli asparaginase 10,000 IU/m2 intramuscularly three times weekly for six and nine doses, respectively, as part of multiagent induction chemotherapy. CSF asparagine levels were measured before, during, and after asparaginase dosing. RESULTS: The percentage of patients with undetectable (< 0.04 micromol/L) CSF asparagine was 3.2% (one of 31 patients) at baseline, 73.9% (17 of 23) during asparaginase therapy, and 56.3% (nine of 16) 1 to 5 days, 43.8% (seven of 16) 6 to 10 days, 20.0% (two of 10) 11 to 30 days and 0% (zero of 21) more than 30 days after asparaginase therapy. The proportion of patients with depleted CSF asparagine was higher during asparaginase therapy than at baseline (P < .001), 11 to 30 days (P = .003), and more than 30 days after asparaginase therapy (P < .001). Median CSF asparagine concentrations were 4.42 micromol/L before, less than 0.04 micromol/L during, and less than 0.04 micromol/L at 1 to 5 days, 1.63 micromol/L at 6 to 10 days, 1.70 micromol/L at 11 to 30 days, and 5.70 micromol/L at more than 30 days after asparaginase therapy, respectively. CSF depletion was more common in patients with low baseline CSF asparagine concentrations (P = .003). CONCLUSION: CSF asparagine concentrations are depleted by conventional doses of E coli asparaginase in the majority of patients, but they rebound once asparaginase therapy is completed.     

Administration schedule of daunorubicin for elderly patients with acute myelogenous leukemia: a single-institute experience

We evaluated the efficacy of daunorubicin (40 mg/m(2)/day for 5 days, 200 mg/m(2)/cycle) combined with standard dose of cytarabine (100 mg/m(2)/day for 7 days) for acute myelogenous leukemia patients aged 65-74 years as induction therapy. Complete remission (81.3%) was achieved in 13 of 16 patients following the therapeutic program. The median duration of recovering absolute neutolophilic counts over 1000/μl and platelet counts over 100 000/μl were 33 days and 27 days, respectively. None of the patients had any adverse cardiac complications or died during administration of the induction therapy. Patients achieving complete remission received post-remission therapy consisting of two regimens other than induction therapy. The 3-year disease-free and overall survival rates were 36.9 and 50.0%, respectively. Extending the total period of the daunorubicin therapy might be an alternative to increasing the daily dose of daunorubicin in the induction therapy for elderly patients who were candidates for receiving intensified chemotherapy.     

Toxicity of combined treatment of adjuvant irradiation and interferon alpha2b in high-risk melanoma patients

Surgically resected stage III melanoma patients commonly receive adjuvant therapy with interferon (IFN) alpha2b. For those patients with high-risk features of draining node recurrence, radiation therapy can also be considered as a treatment option. The purpose of this retrospective study was to assess the efficacy and radiation-related toxicity of this combined therapy. Eighteen patients receiving adjuvant IFNalpha2b therapy during radiation therapy, or within 1 month of its completion, were reviewed retrospectively and analysed for outcome. Radiation was delivered at 600 cGy dose per fraction, in 16 out of 18 patients, twice a week, and at 200 cGy dose per fraction in two patients five times a week. Total radiation dose and number of fractions were as follows: 30 Gy/5 fr (n=8), 36 Gy/6 fr (n=8) and 50 Gy/25 fr (n=2). The percentage of disease-free patients, with no local recurrence, at 3 years was 88%. In 10 patients, IFNalpha2b was administered concurrently with radiotherapy; in three, within 30 days before or after radiation; and in five, more than 30 days after radiation. All the patients experienced acute skin reactions, grade I on the Radiation Therapy Oncology Group (RTOG) scale. Late radiation-related toxicity was seen in one patient with grade III (RTOG) skin reaction and two with grade IV (RTOG) radiation-induced myelitis. Concurrent use of adjuvant radiotherapy and IFNalpha2b might enhance radiation-induced toxicity, and special care should be taken when the spinal cord is included in the radiation field.     

Duration of hospitalization as a measure of cost on Children's Cancer Group acute lymphoblastic leukemia studies.

PURPOSE: We used duration of hospitalization as a surrogate for cost and event-free survival as a measure of effectiveness to estimate the cost-effectiveness ratios of various treatment regimens on Children's Cancer Group trials for acute lymphoblastic leukemia. PATIENTS AND METHODS: The analyses included 4,986 children (2 to 21 years of age) with newly diagnosed acute lymphoblastic leukemia enrolled onto risk-adjusted protocols between 1988 and 1995. Analyses were based on a model of 100 patients. The marginal cost-effectiveness ratio (hospital days per additional patient surviving event-free) was the difference in total duration of hospitalization divided by the difference in number of event-free survivors at 5 years for two regimens. Relapse-adjusted marginal cost of frontline therapy was the difference in total duration of hospitalization for frontline therapy plus relapse therapy divided by the difference in number of event-free survivors at 5 years on the frontline therapy for two regimens. RESULTS: One or two delayed intensification (DI) phases, augmented therapy, and dexamethasone all improved outcome. Marginal cost-effectiveness of these regimens compared with the control regimens was 133 days per patient for DI, 117 days per patient for double DI, and 41 days per patient for augmented therapy. Dexamethasone resulted in 17 fewer days per patient. Relapse-adjusted marginal costs were 68 days per patient for DI and 52 days for double DI. Augmented therapy and dexamethasone-based therapy resulted in 16 and 82 fewer hospital days, respectively. The estimated cost-effectiveness for treating any first relapse was 250 days per patient. CONCLUSION: DI, double DI, augmented therapy, and dexamethasone-based therapy are cost-effective strategies compared with current treatment of first relapse.     

Bleomycin, cyclophosphamide and radiotherapy in regionally advanced epidermoid carcinoma of the head and neck

We have treated 24 patients with squamous carcinoma of the head and neck and advanced regional (N2-3) disease. The regimen consisted of 3 cycles, each of 28 days. Cyclophosphamide (1 gm/m2 I.V.) was given on day 1, bleomycin (15 u I.M.) on days 2, 4, 9 and 11, and ionizing radiation (60Co, 180 rad/fraction) days 1-5, and 8-12. No therapy was given on days 13-28. After three cycles of therapy, 13 patients had a complete response; following further therapy (surgery, interstitial or external beam radiation), 16 patients were free of disease. However, remissions were not durable and 11/16 patients recurred loco-regionally with a median time to recurrence of 5 months; most (7/11 also developed distant metastases. These patients have biologically aggressive disease and may have a worse prognosis than patients who are Stage IV based on a T4 primary lesion only.     

High-dose cytarabine and mitoxantrone in consolidation therapy for acute promyelocytic leukemia.

The objective of our study was to evaluate high-dose cytarabine in consolidation therapy in patients with newly diagnosed acute promyelocytic leukemia (APL). Patients (age 16-60 years) received induction therapy according to the AIDA protocol (all-trans retinoic acid, idarubicin) followed by one cycle of ICE (idarubicin, cytarabine, etoposide) and two cycles of HAM (cytarabine 3 g/m(2) q12h, days 1-3; mitoxantrone 10 mg/m(2), days 2 and 3). From 1995 to 2003, 82 patients were enrolled. In total, 72 patients (88%) achieved a complete remission, and 10 patients (12%) died from early/hypoplastic death (ED/HD). A total of 71 patients received at least one cycle of HAM. Relapse-free survival (RFS) and overall survival (OS) after 46 months were 83 and 82%, respectively. White blood cell count above 10.0 x 10(9)/l at diagnosis and additional chromosomal aberrations were unfavorable prognostic markers for OS, whereas no prognostic markers for RFS were identified including FLT3 mutations. In conclusion, high-dose cytarabine in consolidation therapy for patients with newly diagnosed APL is an effective treatment approach.     

Treatment of Acute Myeloid Leukaemia with Early Intensive Induction Therapy

Patients with primary acute myeloid leukaemia were treated with induction therapy consisting of daunorubicin 50 mg/m² (days 1 and 2) and continuous cytosine arabinoside 400 mg/m² (days 1-5) with a 7-10-day gap between courses. Consolidation therapy consisted of one further similar course and a final course of cytosine 1 g/m² infusion (days 1-5). Patients were randomised to receive no further treatment or monthly maintenance therapy consisting of thioguanine 100 mg/m² twice daily and etoposide 100 mg/m² twice daily (days 1-5) alternating with CCNU 50 mg/m² once to a total of 6 courses. 64 patients entered the study; median age was 54 years (range 18-74 years) and 51 patients entered complete remission (79.7%). Thirty-two patients completed consolidation and were randomised between maintenance therapy (n=16) and no treatment (n=16). 21 patients have relapsed with neither remission duration nor relapse rate being affected by maintenance therapy.     

Typhlitis (neutropenic enterocolitis) after a single dose of vinorelbine

We report a case of a 50-year-old man with pretreated adenocarcinoma of the lung, who developed fatal neutropenic enterocolitis (typhlitis) after a standard dose of the cytotoxic drug vinorelbine. Blood cultures were negative for all microorganisms tested for. Stool cultures were negative for enteric rods but direct examination of fresh stool revealed the presence of Giardia lamblia. Abdominal pain and diarrhoea developed very rapidly while the patient was only moderately neutropenic. Metronidazole was prescribed without clinical benefit: the abdominal pain remained stable. The duration of neutropenia was very short (4 days). The abdominal catastrophe ending in shock occurred after complete recovery of the neutrophil count. Neutropenic colitis has been reported with increasing frequency in solid tumours after the introduction of taxanes. This complication has been observed mainly in phase I studies, near the maximally tolerated doses (MTD). The combined use of vinorelbine has recently been reported to exacerbate the toxic effects of taxane on the colon. The case presented here demonstrates that typhlitis can occur even with vinorelbine alone, used at a standard recommended dose (30 mg/m2).     

Treatment of unresectable pancreatic carcinoma using irradiation with concurrent intravenous 5-FU infusion therapy

Ten patients with unresectable carcinoma of the pancreas who had only bypass surgery to relieve biliary obstruction were treated with radiation therapy to the pancreas and liver with concurrent 5-fluorouracil (5-FU) intravenous infusion therapy. Treatment regimen was three cycles of chemoradiotherapy with a two week rest period between cycles. 5-FU (1,000 mg/m2 per day) was administered by continuous infusion for the first five days of each cycle. In the first cycle radiotherapy was given to the pancreas to 2,000 cGy/10 fractions using 6 to 10 mV x-rays. In the second cycle 2,400 cGy/160 rads/fraction radiation was delivered to the pancreas and whole liver. In the third cycle, 1,600 cGy/160 rads/fraction to a total dose of 6,000 rads, was administered to the pancreatic tumor. All ten patients completed the treatments without interruption. No major side effects were noticed during the course of treatment. Survival ranged from 9 to 16 months and median survival was 11 months. Symptomatic relief was obtained in all 10 patients. One patient who lived for 16 months developed duodenal stenosis and underwent gastrojejunostomy.