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At least 1,243 records · Page 69Linked to original sources

The use of anti-D to improve post-transfusion platelet response: a randomized trial.

Patients undergoing induction chemotherapy for acute leukaemia often become refractory to platelet transfusions. Increased clearance of transfused platelets due to alloimmune destruction has been identified as one of the primary mechanisms contributing to this refractory state. We performed a double-blind randomized trial to determine whether the administration of anti-D to Rh-positive individuals could prevent the refractory state and improve post-transfusion platelet response. Rh-positive patients with acute leukaemia undergoing induction chemotherapy and requiring platelet transfusions were allocated to weekly intravenous anti-D (20 micrograms/kg) or placebo. Platelets and red cell concentrates were administered according to standardized transfusion guidelines. Outcome measures included platelet transfusion utilization, red cell utilization, platelet recovery 18-24 h post-infusion, and the percentage of patients refractory to platelet transfusion. There were 43 patients studied: 21 received anti-D and 22 saline placebo. The mean number of platelet concentrates required per day of observation was 0.59 (SD 0.22) in the anti-D group and 0.61 (SD 0.22) in the placebo group, P = 0.86. No difference was detected between groups in terms of platelet recovery post-infusion, refractoriness to platelet transfusion or frequency of infection (P = 0.97). Red cell concentrate utilization was significantly increased in the anti-D group compared to the placebo group, 0.58 units per day versus 0.37 units per day respectively, P = 0.005. We conclude that the use of anti-D did not improve post-transfusion platelet response in Rh positive patients with acute leukaemia, but did result in an increased need for red cell transfusion.

Acute Disease↗

Randomized trial of neoadjuvant cisplatin and fluorouracil versus carboplatin and fluorouracil in patients with stage IV-M0 head and neck cancer.

PURPOSE: A randomized trial was designed to compare cisplatin (CDDP) and fluorouracil (FU) versus carboplatin (CBDCA) and FU as neoadjuvant treatment in stage IV-M0 head and neck cancer to assess whether CBDCA-FU is better than CDDP-FU with regard to response and toxicity. PATIENTS AND METHODS: Patients were randomized to receive CDDP 100 mg/m2 intravenously on day 1 and FU 5,000 mg/m2 over a 120-hour continuous infusion, or CBDCA 400 mg/m2 over a 24-hour continuous infusion on day 1 and FU with the same schedule. Both regimens were repeated every 21 days. The patients received three courses of chemotherapy, excluding those who failed to achieve a partial response (PR) after the second course. Complete responders were treated with radiotherapy. The remaining patients underwent surgery if the tumor was resectable. RESULTS: Interim analysis was performed when 95 patients were included. The trial was stopped due to significantly better results in the control arm. Differences in response (P = .04) were favorable to CDDP-FU. Hematologic toxicity predominated in the CBDCA-FU arm (P < .001). Mucositis and vomiting predominated in the CDDP-FU arm (P = .03, P < .001, respectively). Favorable outcomes (complete response [CR] plus any grade of toxicity and PR plus grade 0 to 3 toxicity) predominated in the CDDP-FU arm (P = .02). Only the treatment assigned was associated with response (P = .02) and favorable outcomes (P = .009) in the logistic regression analysis. In the CDDP-FU arm, disease-free and overall survival were significantly better. Cox regression analysis showed that only treatment association with disease-free survival remains significant. CONCLUSION: Our results indicate that CDDP-FU is more effective than CBDCA-FU as neoadjuvant treatment in stage IV-M0 head and neck cancer.

Adult↗

Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy for stage II breast cancer: a prospective randomized trial.

BACKGROUND: Preoperative chemotherapy for stage II breast cancer may reduce locoregional tumors and provides initial treatment for systemic micrometastases. We conducted a prospective, randomized trial to evaluate the ability of intensive preoperative chemotherapy to enhance the outcome of this approach. METHODS: Patients with clinical stage II breast cancer (T2N0, T1N1, and T2N1) were prospectively randomized to receive either preoperative or postoperative chemotherapy with five 21-day cycles of fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamide (FLAC)/granulocyte-colony-stimulating factor. Local therapy consisted of modified radical mastectomy or segmentectomy/axillary dissection/breast radiotherapy, according to patient preference. RESULTS: Fifty-three women were randomized (26 preoperative chemotherapy and 27 postoperative chemotherapy). The objective clinical response rate of the primary tumor to preoperative chemotherapy was 80%, and the pathologic complete response rate was 20%. Preoperative chemotherapy reduced the overall incidence and number of axillary lymph node metastases. There was no difference in the use of breast-conserving local therapy between the two treatment arms. There were 20 local/regional or distant recurrences (9 preoperative and 11 postoperative). There was no difference in the overall or disease-free survival between the preoperative and postoperative chemotherapy arms. CONCLUSIONS: Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy was effective against local/regional tumors in stage II breast cancer but was otherwise comparable to postoperative chemotherapy.

Adult↗

GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Gruppo Italiano Valutazione Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon.

BACKGROUND: In 1989, the authors began a randomized trial to determine whether 5-fluorouracil and high dose folinic acid (HD-FUFA) would increase the event free and overall survival of patients with resectable Dukes B and C (AJCC/UICC Stage II and Stage III) colon carcinoma, and to assess the toxicity of the treatment and its impact on selected health-related quality-of-life indicators. Early results were published as a part of an international multicenter pooled analysis (IMPACT) in 1995. The purpose of this report is to update the survival data for patients enrolled in the trial and describe their reported perceptions of their own health and quality of life. METHODS: The trial involved multiple treatment centers, with a centralized randomization between surgery alone and surgery with chemotherapy. The HD-FUFA regimen employed consisted of 5-fluorouracil (370 mg/m2) plus folinic acid (200 mg/m2) administered daily for 5 days every 4 weeks for 6 cycles. Patients' perceptions of their own health status were obtained by means of 3 self-administered questionnaires, which were completed by patients at the time of discharge from the treatment center and at 6 and 24 months after randomization. RESULTS: Overall, 888 patients with resected Dukes B2 and C colon carcinoma were enrolled in the trial. HD-FUFA significantly reduced mortality by 25% (95% confidence interval, 5-41%; P=0.02) and events by 31% (95% confidence interval, 14-45%; P < or = 0.001). Compliance with treatment was good; more than 80% of patients completed the planned therapy. Toxicity was mild, and oral mucositis was the main side effect. None of the health-related quality-of-life parameters investigated (emotional status, worry about the future, changes in social life, impact of the disease, follow-up, and global quality of life) seemed to be affected by the treatment to which patients were allocated. A positive trend in the evolution of patients' psychologic status was observed. CONCLUSIONS: Long term results of this SITAC study confirm that HD-FUFA is a well-tolerated, effective 6-month adjuvant regimen for patients with colon carcinoma that has no detrimental effect on their quality of life.

Adult↗

[A prospective randomized trial of adjuvant chemotherapy with UFT for head and neck carcinoma. Head and Neck UFT Study Group].

A prospective randomized trial was performed in 67 institutions for the purpose to evaluate the efficacy of adjuvant chemotherapy after radical treatment of head and neck carcinoma. A comparison was made between the following two groups; one-year oral administration of UFT, 300 mg/day, after radical treatment (UFT group); and a non-treatment group. Patients were classified under the following three categories; 1) stage II-IV, receiving radical surgery; 2) stage II, receiving radical radiotherapy; and 3) nasopharyngeal cancer. The numbers of cases were 424, 111 and 25, respectively, and they were randomized into two groups. The numbers of eligible cases were 398, 105 and 25, respectively. Statistical analysis was performed in the cases receiving radical surgery and in those receiving radical radiotherapy. As the results, in cases receiving radical surgery no significant difference was observed in 3-year survival rates (77.9% for UFT group vs 72.9% for non-treatment group) or 3-year relapse-free rates (73.4% for UFT group vs 66.2% for non-treatment group) between the two groups. However, the distant relapse rate was significantly lower in the UFT group than in the non-treatment group (7.9% vs 14.6%; p = 0.034). In the cases receiving radical radiotherapy, no significant differences was observed in either 3-year survival rates or 3-year relapse-free rates. Thus it was suggested that UFT maintenance therapy might suppress the distant metastasis after radical surgery. We considered a further confirmative trial for patients at high risk of distant metastasis after radical surgery to be advisable.

Administration, Oral↗

Duodenum-preserving resection of the head of the pancreas in chronic pancreatitis. A prospective, randomized trial.

OBJECTIVE: Two techniques of duodenum-preserving resection of the head of the pancreas were compared in a prospective, randomized trial. The technical feasibility and effects on quality of life were assessed. SUMMARY BACKGROUND DATA: Drainage and resection are the principles of surgery in chronic pancreatitis. The techniques of duodenum-preserving resection of the head of the pancreas as described by Berger and Frey combine both to different degrees. The efficacy of both procedures has not been compared thus far. METHODS: Forty-two patients were allocated randomly to either Beger's (n = 20) or Frey's (n = 22) group. In addition to routine pancreatic diagnostic work-up, a multidimensional psychometric quality-of-life questionnaire and and a pain score were used. Assessment of endocrine and exocrine function included oral glucose tolerance test, serum concentrations of insulin, C-peptide, and HbA1c, as well as fecal chymotrypsin and pancreolauryl test. The interval between symptoms and surgery ranged from 12 months to 12 years, with a mean of 5.7 years. The mean follow-up was 1.5 years. RESULTS: There was no mortality. Overall morbidity was 14% (20% Beger, 9% Frey). Complications from adjacent organs were resolved definitively in 94% (90% Beger, 100% Frey). A decrease of 95% and 94% of the pain score after Beger's and Frey's procedure, respectively, and an increase of 67% of the overall quality-of-life index in both groups were observed. Endocrine and exocrine function did not differ between both groups. CONCLUSIONS: Both techniques of duodenum-preserving resection of the head of the pancreas are equally safe and effective with regard to pain relief, improvement of quality of life, and definitive control of complications affecting adjacent organs. Neither procedure leads to further deterioration of endocrine and exocrine pancreatic function.

Chronic Disease↗

Minicholecystectomy vs conventional cholecystectomy: a prospective randomized trial--implications in the laparoscopic era.

The objective of this study was to compare results of elective "open" conventional cholecystectomy (CC) to those of minicholecystectomy (MC). A clinical prospective, randomized trial was designed. The setting was an academic general surgical unit. In the CC group were 26 patients; in the MC group were 24 patients. In the CC group a conventional open cholecystectomy was performed through a subcostal incision; in the MC group operation through an initial 5-cm subcostal incision was done. Mean length of wound was 14.4 cm and 5.4 cm in the two groups, respectively (p < 0.001). Mean operative time was 60 and 59 minutes, respectively. Mean operative difficulty, estimated on a 1-10 scale, was 3.4 and 5.6, respectively (p < 0.05). Mean postoperative analgesia requirements (number of doses of 10 mg morphine sulphate) were 5.8 and 4.0, respectively (p = 0.002). Mean duration of hospitalization was 4.7 and 3.0 days, respectively (p < 0.001). Mean "overall patient satisfaction," estimated on 1-10 scale, was 6 and 8.3, respectively (p = 0.002). We conclude that Minicholecystectomy offers less pain, earlier recovery, and better cosmetic results than the conventional "open" procedure. Published results of MC compare favorably with those of laparoscopic procedures. The implications of these results in the "laparoscopic era" are discussed.

Cholecystectomy↗

Endocrine-metabolic response to abdominal aortic surgery: a randomized trial of general anesthesia versus general plus epidural anesthesia.

The influence of epidural anesthesia on the endocrine-metabolic response following abdominal aortic reconstruction was studied in a prospective randomized trial. Cortisol and catecholamine responses and nitrogen balance were measured in two groups of five patients receiving general anesthesia only (group 1) or general anesthesia combined with epidural bupivacaine (group 2). The study lasted from preoperatively until the first postoperative day. At 2100 hours on the day of surgery serum cortisol concentrations were higher in group 1 than in group 2 (1.41 versus 0.82 mumol/L; p < 0.01). Likewise the total perioperative hypercortisolemia, expressed as the area under the curve, was significantly higher in group 1 (11.7 versus 5.7 mumol/L/hr, p < 0.01). Intraoperative urinary excretion of epinephrine and postoperative norepinephrine excretion were significantly higher in group 1 than in group 2. Urinary excretion of free cortisol and cumulative nitrogen balance were not different between the groups. Although the number of patients was limited and the sensory nerve block level was not measured perioperatively, this study suggests that epidural anesthesia attenuates the stress response to aortic surgery.

Aged↗

Randomized trial of chemoimmunotherapy in advanced non-oat-cell lung cancer.

Thirty patients without any prior chemotherapy and histologically proved non-oat-cell advanced lung cancer entered a randomized trial comparing a combination chemotherapeutic regimen (cyclophosphamide, methotrexate, BCNU) and the same combination plus intradermic BCG. Twenty-nine patients were evaluable for survival. Mean survival was 11 and 3.5 months for chemotherapy and chemoimmunotherapy group, respectively. The difference was statistically significant (P less than 0.025). A tumor enhancement can be postulated. Skin tests before treatment (PPD, Candida, Varidase) seem to be prognostic for survival.

Adenocarcinoma↗

Randomized trial of FK 506/prednisone vs FK 506/azathioprine/prednisone after renal transplantation: preliminary report.

FK 506 was used as a primary immunosuppressive agent in 125 cases of renal transplantation in a randomized trial comparing FK 506/prednisone with FK 506/azathioprine/prednisone. With a mean follow-up of 5.5 +/- 2.5 months, there has been a 6-month actuarial patient survival of 99% and graft survival of 88%. There is no difference thus far between the two-drug and three-drug groups, although there may be less rejection and diabetes in the three-drug group. These results suggest that FK 506 is a useful immunosuppressive agent in kidney transplantation.

Actuarial Analysis↗

Sulfasalazine has a better efficacy/toxicity profile than auranofin--evidence from a 5 year prospective, randomized trial.

OBJECTIVE: To compare results of medium to longterm sulfasalazine and auranofin treatment in active rheumatoid arthritis (RA). METHODS: 200 patients with active RA were enrolled in a prospective, randomized trial comparing sulfasalazine (target dosage, 40 mg/kg/day) with auranofin (6-9 mg/day). Patients were assessed annually for 5 years, using clinical and laboratory measures of disease activity. Risk of discontinuing treatment was compared using life table analysis. RESULTS: 31% of patients continued sulfasalazine for at least 5 years, compared to only 15% continuing auranofin (p < 0.05). Patients previously given intramuscular (i.m.) gold did particularly badly during auranofin treatment (only 1/26 continued therapy for 5 years), but after excluding all patients previously treated with i.m. gold from both groups more patients continued sulfasalazine for > 5 years (p < 0.05). Patients continuing therapy at 5 years had significantly milder disease at enrollment than those who did not. The patients continuing auranofin treatment at 5 years were no better than at the outset of the trial, and may represent a subgroup of patients with a good prognosis. Patients continuing sulfasalazine, however, showed sustained response over the 5 year period. CONCLUSION: Sulfasalazine therapy was more likely to be continued for 5 years, suggesting better tolerability and/or efficacy than auranofin, and produced evidence of continuing benefit. Patients previously withdrawn from i.m. gold therapy because of inefficacy or minor toxicity should not be given auranofin therapy.

Antirheumatic Agents↗

Clomiphene citrate monitoring for intrauterine insemination timing: a randomized trial.

OBJECTIVE: To compare pregnancy rates with two different methods of intrauterine insemination (IUI) timing in patients treated with clomiphene citrate (CC). DESIGN: Prospective, randomized trial. SETTING: Academic medical center. PATIENT(S): One hundred fifty ovulatory, infertile women. INTERVENTION(S): Patients were randomized into a luteinizing hormone (LH) surge group or a follicle monitoring/human chorionic gonadotropin (hCG) group. All patients underwent baseline ultrasound, and took clomiphene citrate, during days 5-9. Patients in the LH surge group underwent IUI on the day after a home test for the LH surge was positive, whereas those in the hCG group received hCG according to ultrasound parameters and underwent insemination 33-40 hours later. Patients remained in the same study group for up to three cycles. MAIN OUTCOME MEASURE(S): Pregnancy rates per cycle and per patient. RESULT(S): No significant differences were found between groups in pregnancy rates per patient or per cycle. The LH surge group underwent IUI significantly later than the hCG group. Cancellation rates were significantly higher for the LH surge group (31% vs. 11%) and attributable mainly to failure to detect an LH surge. The majority of pregnancies in both treatment groups occurred in the first cycle. CONCLUSION(S): The decision to use hCG for IUI timing should be influenced by factors other than pregnancy rates.

Adult↗

Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials: Chronic Myeloid Leukemia Trialists' Collaborative Group.

BACKGROUND: Several randomized clinical trials in chronic myeloid leukemia (CML) have reported better patient survival with interferon alfa (IFN alpha) than with standard chemotherapeutic agents, such as busulfan or hydroxyurea. However, the size and persistence of this survival benefit is uncertain. Our aim was to assess these reliably, both overall and in particular patient subgroups. METHODS: We collaborated in a worldwide overview of all clinical trials in which patients with CML were randomly assigned to receive either IFN alpha as the main drug or standard chemotherapy. Trials were identified by electronic and hand searching of the medical literature and databases and by personal contact. Individual patient data were available for each of 1554 patients who had been randomly assigned to treatment in seven trials (German, Italian, British, French, Japanese, and "Benelux"). Intention-to-treat stratified logrank survival analyses were performed, reporting two-sided P values. RESULTS: Almost all of the patients in these trials had disease with the Philadelphia chromosome abnormality. Among those who did, the regimens that involved IFN alpha produced a statistically significantly better survival than those involving either hydroxyurea (P = .001) or busulfan (P = .00007) alone. The 5-year survival rates were 57% with IFN alpha and 42% with chemotherapy, with an absolute difference of 15% (standard deviation = 3%; P<.00001). There were no trials or subgroups of patients in which the treatment difference was statistically significantly different from the average. CONCLUSION: For patients with Philadelphia chromosome-positive chronic myeloid leukemia, the inclusion of IFN alpha in the therapeutic regimen produced substantially better 5-year survival than standard chemotherapy alone.

Antineoplastic Agents, Alkylating↗

The effect of monophasic combinations of ethinyl estradiol and norethindrone on gonadotropins, androgens and sex hormone binding globulin: a randomized trial.

The effects of different monophasic combinations of ethinyl estradiol and norethindrone on FSH, LH, sex hormone binding globulin, total testosterone, androstenedione, and dehydroepiandrosterone sulfate levels in non-obese, non-hirsute women were compared. Retrospective analysis of frozen serum from a prospective randomized trial in which women received one of three oral contraceptive pills containing ethinyl estradiol 50 micrograms/norethindrone 1 mg, ethinyl estradiol 35 micrograms/norethindrone 1 mg or ethinyl estradiol 35 g/norethindrone 0.5 mg for nine cycles was conducted. Blood samples were obtained prior to treatment and during the third, sixth and ninth pill cycles. Ethinyl estradiol 50 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 1 mg suppressed FSH, LH, and total testosterone and increased sex hormone binding globulin to a similar degree. Ethinyl estradiol 35 micrograms/norethindrone 0.5 mg resulted in less suppression of FSH, LH, and total testosterone, but greater elevation of sex hormone binding globulin. Dehydroepiandrosterone sulfate was suppressed to a similar degree with ethinyl estradiol 35 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 0.5 mg, but ethinyl estradiol 50 micrograms/norethindrone 1 mg resulted in the least suppression of dehydroepiandrosterone sulfate. Ethinyl estradiol 35 micrograms/norethindrone 1 mg caused greater suppression of androstenedione than did the other two oral contraceptives. Oral contraceptive-induced changes in gonadotropins, androgens, and sex hormone binding globulin can be predicted by considering the relative amounts of estrogen and progestin in the pill. When combined with 1 mg of norethindrone, 50 micrograms of ethinyl estradiol did not result in greater suppression of FSH, LH, or total testosterone or in greater elevation of sex hormone binding globulin than did 35 micrograms of ethinyl estradiol.

Adolescent↗

A randomized trial to evaluate a computer-based learning program in occupational lung disease.

Computer based learning (CBL) is a recent educational innovation that may supplement the limited formal education typically offered to medical students in occupational health-related issues. The authors conducted a randomized trial among sophomores to evaluate a Macintosh-based application on occupational lung disease (OH-CBL). The program emphasizes interactive learning and skills practice through a case-based approach. Students taking an OH block in the Preventive Medicine course were assigned either to the OH-CBL or to the lecture group. 35 students completed the OH-CBL; 45 attended the lecture. Of four study-relevant multiple-choice questions, substantial differences were found in favor of the OH-CBL group over the lecture group on one question as well as on the study-relevant multiple choice total score. There was no difference on mean overall grade or on the three study-relevant essay items. The grade on study-relevant questions exhibited a weak relationship with microcomputer experience (r = .29, P = .04). Students' ratings of the CBL program using Likert scales were generally favorable. These findings suggest that CBL programs can be designed to be both acceptable to students and educationally effective. Each new program needs to be individually assessed to meet these standards. The authors identify several components of CBL that are necessary for successful implementation into a medical curriculum.

Computer-Assisted Instruction↗

An overview of the 4 randomized trials of aspirin therapy in the primary prevention of vascular disease.

BACKGROUND: In the primary prevention of cardiovascular disease, in contrast to the recommendations of the American College of Chest Physicians and the American Heart Association, the US Food and Drug Administration recently stated that there was insufficient evidence to judge whether aspirin therapy decreases the risk of a first myocardial infarction. OBJECTIVE: To perform an overview of the 4 primary prevention trials of aspirin therapy to obtain the most reliable estimates of the effects of aspirin therapy on various vascular disease end points. METHODS AND RESULTS: These 4 trials included more than 51,000 subjects and 2284 important vascular events. Those assigned to aspirin therapy experienced significant reductions of 32% (95% confidence interval [CI], 21%-41%) for nonfatal myocardial infarction and 13% (95% CI, 5%-19%) for any important vascular event. There were possible small but nonsignificant increases in risks of vascular disease-related death (1%; 95% CI, -12% to 16%) and nonfatal stroke (8%; 95% CI, -12% to 33%). When strokes were subdivided by type, there was no significant effect of aspirin therapy on the risk of ischemic stroke, but, while based on small numbers, there was a 1.7-fold apparent increase (95% CI, 6%-269%) in the risk of hemorrhagic stroke, which did achieve statistical significance. CONCLUSIONS: For the primary prevention of vascular disease, aspirin therapy confers significant beneficial effects on first myocardial infarction and, as a result, on any important vascular event; these effects are clinically important. Whether there is any reduction in vascular disease-related death or stroke associated with treatment remains unclear because of inadequate numbers of events in the primary prevention trials completed to date. More data on hemorrhagic stroke are also needed. In addition, randomized trial data, especially in women but also in men, are needed to help to formulate a rational public health policy for individuals at usual risk. Meanwhile, these data provide evidence for a significant benefit of aspirin therapy in the primary prevention of myocardial infarction.

Adult↗

A prospective randomized trial of matching for HLA-A and B versus HLA-DR in renal transplantation.

A prospective randomized trial was performed comparing survival of cadaveric grafts allocated by HLA-A+B matching and HLA-DR matching. The two allocation methods resulted in very similar graft survivals. HLA-A matching had no significant effect on graft survival. HLA-B and HLA-DR matching were shown to have approximately equal, significant, independent, and additive effects on graft survival. Other factors that were demonstrated to have significant effects were blood transfusion, preformed antibodies, graft number, and recipient sex. The results indicate that neither allocation method alone is optimal, and that matching for HLA-B+DR is necessary. However a large pool size is necessary to obtain a high frequency of good matches.

Adolescent↗

Recent randomized trials of chemoradiation in the management of locally advanced head and neck cancer.

The use of concurrent chemotherapy and radiation, or chemoradiation, has become the focus of increasing interest in the management of patients with squamous-cell head and neck cancer. Randomized trials comparing radiation therapy alone with radiation and single chemotherapeutic agents given concurrently have suggested benefit for several different drugs. Randomized multiagent chemoradiotherapeutic trials have been approached somewhat more tentatively in view of the anticipated additional toxicity. Nonetheless, several studies have been reported, and a more consistent survival benefit with chemoradiotherapy has been observed. Treatment regimens using rapidly alternating chemotherapy and radiation schedules have also resulted in an improvement in survival. Although these kinds of aggressive treatment approaches produce significant incidences of morbidity and may not be appropriate for all patients, a role for chemoradiotherapy in the definitive management of this disease is being defined.

Antineoplastic Agents↗