Long-term remission after brachytherapy with external irradiation for locally advanced lung cancer

Three cases are reported who received brachytherapy with external irradiation for inoperable lung cancer and have shown long-term remission. The diseases were adenoid cystic carcinoma, recurrent adenocarcinoma and squamous cell carcinoma. The associated symptoms were severe cough and dyspnea in all 3 cases. They received 60 Gy of external irradiation. After an interval of 2 weeks, 6 Gy at a radius of 1 cm from the center of the source was delivered by iridium-192. They received 2-4 fractions at 1-week intervals. On termination of brachytherapy, complete response was observed in all cases. In 1 case, bronchial stenosis due to radiation-induced fibrosis was observed, but was successfully treated by bronchial stent. Cough and dyspnea disappeared, and all patients have been rendered asymptomatic for the last 2 years. Local disease was well controlled in 2 cases; however, minimal local recurrence was observed after a 2-year follow-up in 1 case.     

Arterial infusion chemotherapy of 5-FU and leucovorin for patients with liver metastases from colorectal cancer

Fifteen patients with liver metastases from colorectal cancer were treated by arterial infusion of 5-FU and leucovorin. Two regimens were performed. One was weekly bolus infusion of leucovorin following bolus infusion of 5-FU (bolus group), the other was 5 days continuous infusion of 5-FU and leucovorin in 3 weeks (continuous group). One PR was obtained both in the bolus group and in the continuous groups. The objective response rate was 11% in the bolus group and 20% in the continuous group. The one- and 2-year survival rates for these patients were 40% and 0% in the bolus group, and 80% and 60% in the continuous group, respectively. These results suggest that continuous arterial infusion of 5-FU and leucovorin was more effective than individual bolus arterial infusion of leucovorin and 5-FU for patients with liver metastases from colorectal cancer.     

High-dose rate iridium192 afterloading therapy in combination with external beam irradiation for localized prostate cancer

The number of donors aged 60 years and over has increased. This study examined discard rates and transplant outcomes in organs recovered from older donors. Data were obtained using a standard tool for donors aged 60 years and older during 1993 and 1994 and included demographics, medical history, use of vasopressors, renal/liver function studies, organ disposition, biopsy findings, and recipient organ function. Of 58 kidneys recovered, 24 were transplanted, 26 were used for research, and 8 were discarded. Of 14 livers recovered, 11 were transplanted, 1 was used for research, and 2 were discarded. Sixty-three percent of kidney recipients had immediate function; 79% at 30 days. Nine liver recipients had immediate function; 6 at 30 days, with 1 graft lost. Results show that kidneys and livers can be transplanted from older donors with positive outcomes. Factors such as medical history, use of vasopressors, and organ function studies may help predict organ disposition and function.     

The evaluation of weekly hepatic arterial infusion of high-dose 5-FU for liver metastases from colorectal cancer

OBJECTIVE: The degree to which patient education in the areas of diet, exercise, and stress management can improve symptoms of irritable bowel syndrome (IBS) through healthier lifestyle behaviors is unknown. The aim of this study was to determine the effects of outpatient education on the short and long term outcomes, and the association between health-promoting behaviors and symptoms. METHODS: Pender's Health Promotion Model provided the theoretical framework. The study had a prospective longitudinal design. A consecutive sample of 52 adult outpatients with IBS attended a structured class that taught health-promoting modifications of lifestyle. Participants completed the Health-Promoting Lifestyle Profile (HPLP) and selected items from a Bowel Disease Questionnaire (BDQ) before the class and 1 month and 6 months later. Spearman rank correlations were used to assess the association between HPLP and symptom scores. Wilcoxon rank sum tests compared changes in scores versus their baseline values. RESULTS: Response rates at 1 and 6 months were 75% and 83%, respectively. Results revealed significant 1- and 6 month-improvements in pain and Manning symptoms (p < 0.01) and in some HPLP scores (exercise at 1 month, p < 0.05; stress management at 6 months, p < 0.01). Significant associations were found between some, but not all, HPLP and symptom scores over time. CONCLUSION: A structured IBS educational class for patients with IBS improved symptoms and some health-promoting behaviors. However, relationships among specific behaviors and specific symptoms did not consistently correspond with this improvement.     

Low-dose CDDP and continuous 5-FU treatment of advanced gastric cancer with peritoneal dissemination: a case with long disease-free survival

The patient was diagnosed to have gastric cancer (T3 N3 M0 P3, Stage IV b). We conducted LcFP therapy. CDDP, 7 mg/m2/day, day 1-5 i.v. drip for 2 hours, and 5-FU, 170 mg/m2/day, day 1-7, i.v. continuously for 24 hours. After 3 courses (one course: 4 LcFPs followed by one rest week), down staging (T3 N2 M0 P1. Stage IV a) and improvement of performance status were obtained, and then surgical resection was undertaken. After operation one course of LcFP therapy served as adjuvant chemotherapy. The patient has survived over one year and 8 months to date in a tumor-free condition. LcFP therapy promises to be useful in the clinical management of advanced gastric cancer.     

Schedule-selective biochemical modulation of 5-fluorouracil: a phase II study in advanced colorectal cancer

Based on experimental findings suggesting that 5-fluorouracil (FUra) may have different mechanisms of action depending on the schedule of administration, we generated the hypothesis that biochemical modulation of this fluoropyrimidine should be schedule specific. We thus tested the activity of a hybrid regimen consisting of two biweekly cycles of FUra bolus (600 mg/m2) modulated by pretreatment (24-h interval) with methotrexate (200 mg/m2), alternating with a 3-week continuous infusion of FUra (200 mg/m2/day) modulated by low-dose (6S)leucovorin (20 mg/m2 bolus weekly). Thirty-three consecutive patients with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study from February 1992 to August 1993. They were treated with two biweekly cycles of FUra bolus (600 mg/m2) preceded by (24-h interval) methotrexate (200 mg/m2), alternating with a 3-week continuous infusion of FUra (200 mg/m2/day) modulated by low-dose (6S)leucovorin (20 mg/m2 bolus weekly). The median Eastern Cooperative Oncology Group performance status was 1; the liver was the only metastatic site in 17 patients. Treatment outcome was evaluated by computed tomographic scan in all patients, except for two. Three complete and 13 partial responses were obtained among these 33 patients (response rate, 48%; 95% confidence limits, 31-66%). Performance status (Eastern Cooperative Oncology Group) influenced clinical response. The combined complete response and partial response rate was 69%, 33%, and 25% in patients with an Eastern Cooperative Oncology Group performance status of 0, 1, and 2, respectively (chi2, 4.6, P = 0.032, two-tailed Mantel test for trend). After a median follow-up time of 26 months, 10 patients are still alive. The median progression-free survival and overall survival were 9.5 and 20.2 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was: mucositis 6%, diarrhea 3%, and vomiting 3% for the bolus part and 21%, 3%, and 6%, respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% of the patients treated with the continuous infusion regimen.     

Treatment of advanced colorectal cancer with folinic acid and 5-fluorouracil in combination with cisplatinum

51 patients with metastatic colorectal cancer (stage Dukes D) were treated with intravenous (i.v.) infusion on days 1, 3, 5, 8 and 16 with folinic acid (200 mg/m2) and 5-fluorouracil (600 mg/m2), and on days 1, 8 and 16 with cisplatinum (25 mg/m2 i.v.); cycles were repeated every 4 weeks. All 51 patients were evaluable for toxicity and response criteria. 26 patients had objective responses (3 complete responses, 5.9%; 23 partial responses, 45.1%), relative risk 51% (95% confidence intervals 36.7-65.0%). Response duration ranged from 4 to 28.0 months (median 16.8). Overall median survival of all patients included was 14.7 months (range 3.0-33.0). Toxicity of WHO grade III, requiring dose reduction, occurred in 9 (18%) patients. The regimen described here appears to be active, safe and well tolerated for treatment of patients with advanced colorectal cancer.     

Early stage vocal cord cancer: results after external beam radiotherapy

Much has been written about suck confusion due to a baby's oral experience with objects other than the breast--but how much difference is there in the relative impacts on a baby's ineffective suck if a teat is used instead of other currently accepted techniques such as cup and finger feeding? Mothers who seek the help of a lactation consultant will commonly already be using bottles and teats as part of their management regime for a difficult situation. Especially if the problems are well developed and complex, many mothers will not be able to accept unfamiliar alternatives such as cup and finger feeding and prefer to wean rather than do so. Current teat designs have evolved with no reference to Woolridge's landmark research published over ten years ago which clearly demonstrated how normal breastfeeding works. Rather, manufacturers offer consumers an array of teats which have been shortened in length and distorted in conformation when compared with teats available thirty years ago which coincidentally were a closer physiological match with the positioning of the nipple and breast tissues in the mouth of a breastfeeding baby than teats designed and produced since then. Fortunately one UK manufacturer still markets this thirty year old style of teat in a flow rate suitable for very young babies. Over a three year period, we at first hesitantly, but with increasing confidence asked mothers to use this teat when suck retraining and supplementation were indicated. We are able to report that use of these teats has resulted in a success rate in excess of 90% converting babies with significant sucking problems into fully effective breastfeeders.     

Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies

In patients with malignant astrocytomas or metastatic brain disease treated with high-dose radiotherapy, conventional imaging methods may not adequately distinguish recurrent tumor from radiation change. We used a fast spoiled gradient refocusing technique in the open-configuration intraoperative MR system to assess the rate of regional enhancement of the treated tumor bed and to localize specific sites for pathologic sampling to determine whether gadolinium uptake correlated with histologic data. Twenty-four patients were studied. Fourteen of 15 patients with areas of early enhancement had recurrent tumor present in histologic samples, and 8 of the remaining 9 patients had only reactive changes. Dynamic MRI was predictive of recurrent tumor (P < .0005, Fisher exact test and P < .002, Student t test). We conclude that dynamic MRI in the open-bore magnet is a promising method for localizing potential sites of active tumor growth in patients treated for malignant astrocytomas and metastatic brain lesions.     

The preventive effect of weekly high-dose 5-FU infusion (WHF) after resection of hepatic metastasis from colorectal cancer

Hepatic metastasis is often found even after resection of hepatic metastases from colorectal cancer. This implies that the micrometastasis already existed in residual liver when the resection was performed, and so complete recovery with resection alone is rare. We have been using a weekly high-dose 5-FU HAI (WHF = 5-FU 1,000 mg/m2/5 hrs/qw) since 1991, which has preventive effects for metastasis in residual liver as compared to a group treated without infusion chemotherapy. Hepatectomy was performed in 30 of 113 cases of hepatic metastasis from colorectal cancer during the past 16 years. For comparison, we divided the 30 cases into group A1 (16 cases H1:12, H2:4), which received hepatectomy only, and group A2 (14 cases H1:8, H2:4, H3:2), which additionally received infusion chemotherapy. The 1- and 3-year (cumulative) survival rates were 64.6% and 32.3% in group A1, and 100% and 75.3% in group A2 respectively in which the treatment outcome was significantly higher. The 1- and 3-year recurrence rates were 41.7 and 66.3 in group A1, and 8.3% each in group A2, respectively, which reveals that metastasis in residual liver was controlled in group A2. Other metastases were seen in lung (6 cases), bone (2 cases), hepatic hilar lymph node (3 cases), brain (1 case) and local (3 cases) in group A1, while only one metastasis in each brain and locally was seen in group A2 so far. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect not only for the recurrence in residual liver but also for other metastases. Therefore, as improvement in the survival rate is expected.     

5-Fluorouracil (5-FU) continuous intravenous infusion compared with bolus administration. Final results of a randomised trial in metastatic colorectal cancer

The aim of this Phase III, balanced randomised trial was to compare continuous intravenous infusion (CVI) of 5-FU with bolus (B) administration for metastatic colorectal cancer (CRC). One hundred and fifty-five non-pretreated patients were randomised to receive CVI 5-FU at a dose of 750 mg/m2/day (d), 7 d every 21 d (n = 77), or bolus 5-FU 500 mg/m2/d x 5 d every 28 d (n = 78). Incremental dose escalation at 50 mg per step was recommended in the absence of toxicity. All the patients had measurable metastatic disease (M), particularly, liver and a good performance status (WHO grade 0-1). Dose intensity was significantly higher in CVI than in the bolus group: 1369 mg/m2/week versus 558 mg/m2/week (P = 0.0001). Grade II-IV stomatitis was more frequent in the CVI group (31% versus 9%; P < 0.0001) as was hand and foot syndrome (14% versus 3%; P < 0.001). Diarrhoea (22% versus 12%) and grade III granulocytopenia (2% versus 6%) were comparable. Responses were more frequent in the CVI (26%) than in the bolus group (13%) (P < 0.04); progression-free survival was higher for the CVI group (P = 0.04), but there was no statistical difference in overall survival (median: 10 months (m) compared to 9 m), and 1 year survival (SD) 42% (6%) versus 40% (6%). In the multivariate analysis, survival was better for patients with a good PS, well-differentiated adenocarcinomas and a primary tumour without serosal extension. In conclusion, with a higher dose intensity, CVI 5-FU improved tumour control, but not overall survival.     

Internal hemipelvectomy with intraoperative and external beam radiotherapy in the limb-sparing treatment of a pelvic girdle chondrosarcoma

The case of a patient with an extensive pelvic girdle chondrosarcoma treated with internal hemipelvectomy and intraoperative radiotherapy, followed by adjuvant high-dose external beam radiotherapy, with a successful attempt in achieving long-term local tumor control and limb-sparing treatment is described.     

Nedaplatin and 5-FU combined with radiation in the treatment for esophageal cancer

A direct differentiation of the internal and external drug-deposition pattern into hair was made using two fluorescent dyes and fluorescence microscopy after systemic administration to mice or external exposure of untreated hair. Mice (23 days old, C57 and Balb/C) were administered either rhodamine or fluorescein intraperitoneally at varied doses on 3 consecutive days of 3 weeks, and hair was sampled 1 week later. Another group was given 10 mg/kg rhodamine or 100 mg/kg fluorescein and sampled at time points from 5 min to 168 hr. The time courses of external deposition of rhodamine and fluorescein into untreated hair were examined after hair was soaked in 0.1 mg/ml solutions at pH 3, pH 6, and pH 9 aqueous buffer or methanol. The hair was then extracted in pH 6 phosphate buffer or methanol for 24 hr. In vivo accumulation was distinguishable as fluorescent bands along the length of the hair for rhodamine and fluorescein. The pattern of in vivo deposition appears to arise from the rapid accumulation within the cortex and medulla, with little deposition evident in the cuticle. Neither phosphate buffer nor methanol washes affected the intensity of fluorescence in the hair. External loading of rhodamine into the hair resulted in staining of the junctions of cuticle scales. This pattern persisted even after 12 hr of solution exposure. Extraction with pH 6 phosphate buffer or methanol did not remove rhodamine. Fluoroscein followed a similar pattern, with maximum fluorescence when hair was loaded in pH 6 100mM phosphate buffer and nominal staining when loaded in pH 9 100 mM Tris buffer or methanol. Soaking the hair in pH 6 buffer, but not methanol, removed some fluorescein. These results demonstrate that compounds in the circulation can rapidly diffuse into the forming cortex and medulla, where rapid associations occur with elongating intermediate filaments specific to the medulla and cortex. These compounds can become significantly occluded within the mature matrix and are resistant to removal in aqueous or methanolic solutions.     

New combination therapy with FTM [5-FU, pirarubicin (THP) and MMC] for treatment of inoperable advanced gastric cancer

Clinical usefulness of a new combination FTM therapy consisting of 5-FU, Pirarubicin (THP) and MMC for the treatment of advanced gastric cancers was investigated. 5-FU, THP or MMC was administered at a dose of 600 mg/m2 on day 1, 8, 22 and 29, 30 mg/m2 on days 1 and 22, and 10 mg/m2 on day one only of each course, respectively. Eighteen patients with inoperable advanced gastric cancer were treated with FTM. All drugs were investigated by intravenously by one shot. The tumor response rate was 50% [9 of 18 showed PR]. The survival rate was higher in responders than in nonresponders (18.1% vs 11.1%) (p < 0.05). Side effects in the gastrointestinal tract were minimal. Cardiotoxicity and nephrotoxicity were not detected, but myelosuppression was prominent in most cases. G-CSF was given in sixteen patients (88%), and platelet transfusion was performed in two patients (11%). New combination FTM therapy is an effective treatment regimen even for advanced inoperable gastric cancer.     

Type-oriented intraoperative and adjuvant chemotherapy and survival after curative resection of advanced gastric cancer

Recent observations and our experience that histologic types of gastric cancer related significantly to patterns of recurrence prompted us to develop intraoperative and postoperative chemotherapy based on the preoperatively diagnosed histologic types of cancer and to evaluate its effectiveness by a prospective randomized trial. This chemotherapy regimen consisted of the intraoperative administration of mitomycin C (MMC) and postoperative administration of cisplatin (80 mg/patient, day 14), and tegaful and uracil (UFT) (300-600 mg/day for 2 years). Patients with a diffuse type of cancer were randomly assigned to one of three treatment groups: no intraoperative chemotherapy and UFT 300 mg/day (P0 group, n = 16); intraoperative chemotherapy and UFT 300 mg/day (P1 group, n = 13); or UFT 600 mg/day (P2 group, n = 17). Patients with an intestinal type of cancer were randomly assigned to one of three treatment groups: H0 (n = 17), H1 (n = 12), and H2 (n = 12); each group was subjected to the same protocols as the P0, P1, and P2 groups, respectively, except for the MMC administration route. MMC (10 mg/patient) was administered intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal vein (H1 and H2 groups). All patients underwent curative resection. Background factors did not differ significantly among the treatment groups. The overall survival rates were progressively worsened in the order of P2, P1, and P0 or H2, H1, and H0, respectively. The survival rate of the P2 group was statistically higher than that of the P0 group (p < 0.05). The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group (p < 0.05) or H0 group (p < 0.05), respectively. These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site.     

Demonstration of hepatic steatosis by computerized tomography in patients receiving 5-fluorouracil-based therapy for advanced colorectal cancer

The frequency and severity of fatty infiltration of the liver in patients receiving 5-fluorouracil (5-FU) and folinic acid has not been documented systematically. Its development can result in difficulty assessing disease progression, and treatment may be altered inappropriately. Twenty-seven patients with colon cancer and liver metastases receiving 5-FU and folinic acid were studied with computerized tomography (CT) before treatment and after six or 12 cycles of chemotherapy. Forty-seven per cent of patients developed hepatic steatosis during treatment. There was no correlation between development of hepatic steatosis and the dose of chemotherapy or the liver function tests. Hepatic steatosis occurs commonly in patients receiving 5-FU and folinic acid and can be severe. Its development can make hepatic metastases difficult to assess and if its benign nature is not appreciated treatment may be inappropriately altered.     

The feasibility of CEF (cyclophosphamide, epirubicin, 5-FU) regimen in the adjuvant setting of primary breast cancer

OBJECTIVE: The assay of dried blood spots on filter paper to determine blood glucose concentration has been used to detect hypoglycaemia in out patients. We assessed the accuracy of this approach in assaying blood glucose concentrations in the hypoglycaemic range. DESIGN: Volunteers were rendered hypoglycaemic by intravenous infusion of insulin. The glucose concentration in simultaneously taken blood samples was measured either fresh or after drying on filter paper. PATIENTS: Twenty-four healthy young volunteers and 9 patients with insulin-dependent diabetes were studied. MEASUREMENTS: Plasma glucose concentrations were measured using a standard auto analyser glucose oxidase method. Whole blood taken simultaneously was placed on prepared filter paper and allowed to dry; glucose concentration was then measured using a well-established technique. A correction factor was applied to convert the glucose concentration of plasma to that of whole blood. The relationship between glucose concentrations measured by the two methods was determined by regression coefficient. RESULTS: In the unequivocally hypoglycaemic range (plasma < or = 2.5 mmol/l), corrected dried blood spot glucose concentrations significantly correlated with standard plasma glucose concentrations (r = 0.81; P < 0.001). The dried blood spot method had a sensitivity of 91%. In the range designated probable hypoglycaemia (plasma < or = 3.3 mmol/l), there was also significant correlation (r = 0.90; P < 0.001) and the sensitivity was 96%. The specificity of the dried blood spot method was 100% in both ranges. CONCLUSIONS: Measurement of glucose concentrations in dried blood spots is specific and sensitive in the hypoglycaemic range. The present study indicates that hypoglycaemia may be excluded or confirmed respectively when levels in excess of 3.7 or below 2.8 mmol/l are found in uncorrected dried blood spot analysis.     

Interleukin 2 and interferon alpha-2a do not improve anti-tumour activity of 5-fluorouracil in advanced colorectal cancer

Treatment using a combination of 5-fluorouracil (5-FU), interferon-alpha (IFN alpha-2a) and interleukin 2 (IL-2) has been shown to mediate disease regression in selected patients with advanced colorectal cancer. This phase II study was designed to evaluate the anti-tumour activity and toxicity of the combination of IL-2, IFN alpha-2a and 5-FU in patients with advanced colorectal cancer. Forty-four patients with metastatic colorectal cancer were treated, predominantly on an outpatient basis, with subcutaneous IFN alpha-2a and IL-2 three times per week followed by once a week bolus intravenous 5-FU injections. There were six (14%) partial responses among the 43 evaluable patients [95% confidence interval (CI) 5-28%]. Twenty-four patients had stable disease (56%) and 13 patients (30%) showed progressive disease. The median time to progressive disease in 43 patients was 19 weeks (range 2-72 weeks) and in responders 34 weeks (range 24-30 weeks). The median overall survival was 47 weeks (range 2-85 weeks) and in responders 60 weeks (range 35-71 weeks). Treatment-related toxic effects included fatigue, nausea and vomiting. Granulocytopenia was the main reason for the dose reductions or treatment interruptions in 32 out of 44 patients. One patient died of toxicity due to renal failure. Serial assessments of immunophenotyping and cytolytic activities of peripheral blood lymphocytes did not show changes in the numbers of circulating natural killer (NK) cells or in the levels of NK and lymphokine-activated killer (LAK) cytolytic activities. This regimen of IL-2 and IFN alpha-2a with 5-FU has only modest anti-tumour activity in advanced colorectal cancer.