Aspiration risk and postoperative radiation for head and neck cancer.

The aim of the study was to assess the aspiration risk following postoperative radiation for head and neck cancer. Thirty-seven patients had Modified Barium Swallow before and following treatment. Dysphagia severity was graded from 1 to 7. Before treatment there were sixteen grade 1, seventeen grade 2, three grade 3 and one grade 5. Following postoperative radiation, two patients had grade 1, eleven patients had grade 2, thirteen patients had grade 3, four patients had grade 4, four patients had grade 5, one patients had grade 6, and two patients had grade 7. Nineteen percent (7/37) of the patients developed aspiration (grade 5-7). Aspiration is life-threatening and may develop for all tumor sites and stages.

Long-term aspiration following treatment for head and neck cancer.

BACKGROUND: Dysphagia and aspiration are long-term complications with life-threatening consequences following treatment of head and neck cancer. We would like to assess the prevalence of aspiration in patients with long-term persistence of dysphagia (1 year or more) following treatment for head and neck cancer and to identify potential risk factors of aspiration. METHODS: Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1-7. RESULTS: Between 1992 and 2004, 74 patients with dysphagia underwent MBS 12-152 months following treatment (median 29 months). There were 2 grade 1, 22 grade 3, 21 grade 4, 11 grade 5, 7 grade 6, and 11 grade 7 cases. Twenty-nine patients (39%) had long-term aspiration at a median follow-up of 25 months (range 12-82). Eighteen patients (24%) required permanent gastrostomy because of severe aspiration. Type of treatment and disease stage did not seem to influence long-term aspiration risk. CONCLUSION: Patients with long-term dysphagia after treatment for head and neck cancer are at risk of aspiration. MBS should be performed to identify these patients.

Dysphagia severity and aspiration following postoperative radiation for locally advanced oropharyngeal cancer.

UNLABELLED: The aim of the present study was to assess dysphagia severity following postoperative radiation for locally advanced oropharyngeal cancer. PATIENTS AND METHODS: Eighteen patients with oropharyngeal carcinoma had undergone postoperative radiation. There were eight base of tongue, eight tonsils, and two soft palate carcinomas. All the patients had undergone modified barium swallow (MBS) to assess the persistence of dysphagia (more than one month) post-treatment. All the patients were cancer-free at the time of the swallowing study. Dysphagia severity was graded as 1-7. RESULTS: At a median follow-up of 12 months, there were three grade 2, four grade 3, two grade 4, five grade 5, two grade 6, and two grade 7. Only three patients (17%) had normal swallow post-treatment. Six patients (33%) had mild to moderate dysphagia (grade 3-4). Nine patients (50%) developed aspiration (grade 5-7). Among the patients who developed aspiration, four (22%) required tube feeding for severe aspiration. CONCLUSION: Long-term (more than one year) dysphagia following postoperative radiation for oropharyngeal cancer may be symptomatic of permanent damage to the swallowing mechanism. Evaluation of patients who complain of persistence of dysphagia a year or more following treatment should include MBS, because of the increased risk of aspiration.

Impact of swallowing therapy on aspiration rate following treatment for locally advanced head and neck cancer.

This study examines the efficacy of swallowing therapy in cancer-free patients who developed aspiration following treatment for locally advanced head and neck cancer. The records of 41 patients who underwent swallowing therapy for aspiration were reviewed. All patients were cancer free at a median follow-up of 25 months (6-150 months). Their treatment were respectively chemoradiation (24), and postoperative radiation (17). All patients had two or more modified barium swallow (MBS). Dysphagia severity was graded from 1 to 7. Dysphagia grade was compared before and following swallowing therapy. Before swallowing therapy, there were 16 grade 5 (trace aspiration), and 25 grade 6-7 (severe aspiration). In the chemoradiation group, there were nine grade 5, five grade 6, and 10 grade 7. Corresponding numbers for the postoperative group were: seven grade 5, seven grade 6, and three grade 7. Following swallowing therapy, there were six grade 3, seven grade 4, 10 grade 5, six grade 6, and 12 grade 7. In the chemoradiation group, there were four grade 3, three grade 4, four grade 5, five grade 6, and eight grade 7. In the postoperative group, there were two grade 3, four grade 4, six grade 5, one grade 6, and four grade 7. Overall, 13 patients (32%) had improvement of their dysphagia severity. Seven of them were in the chemoradiation group (29%), and six (35%) were in the postoperative group. Among 25 patients who presented with grade 6-7 aspiration, only nine (36%) improved to grade 5 or less. Four of them (27%) were in the chemoradiation group, and five (29%) were in the postoperative group. Swallowing therapy is effective to improve dysphagia severity and reduce the need for tube feedings. However, a significant number of patients still suffered from chronic severe aspiration. New strategies must be devised to improve their outcome.

Aspiration occurence during chemoradiation for head and neck cancer.

AIM: To assess the risk of developing aspiration during chemoradiation for head and neck cancer. PATIENTS AND METHODS: A retrospective review of 114 patients who underwent concurrent chemoradiation for locally advanced head and neck cancer was undertaken. Patients were determined as having aspiration if they had pneumonia on chest-X-ray (CXR) and/or had documented aspiration on the modified barium swallow (MBS) during their treatment. RESULTS: Fifteen patients (13%) developed aspiration during chemoradiation. Twelve patients (10%) had aspiration demonstrated on CXR alone (9 patients) or combined with MBS (3 patients). Three patients (3%) had aspiration on MBS alone. Three of the six patients with aspiration observed on MBS had normal swallowing on their pretreatment MBS. All 15 patients had severe mucositis and neutropenia at the time of the aspiration. Despite broad-spectrum antibiotics and supportive care, six patients (5%) died. CONCLUSION: Aspiration may develop during chemoradiation for head and neck cancer because of radiation-induced altered swallow.

Evaluation and management of swallowing dysfunction following chemoradiation for head and neck cancer.

PURPOSE OF REVIEW: Concurrent chemoradiation offers excellent local control and survival for patients with locally advanced head and neck cancer while allowing anatomic organ preservation. Treatment toxicity is significant, however, often resulting in long-term dysphagia and aspiration. We review the prevalence of post-treatment swallowing dysfunction, describe current thinking about its pathogenesis and management, and signal possible directions for future research. RECENT FINDINGS: Apoptosis from chemoradiation induces abnormal motility of the upper aerodigestive tract, resulting in stasis of the bolus in all phases of the swallow, and resulting in aspiration when the larynx is not protected during swallow. Long-term scarring may result in stenosis of the upper digestive tract. Recent findings suggest the role of transforming growth factor beta 1 in the pathogenesis of normal tissue damage and late scarring induced by radiation. Aspiration is often silent, and therefore a modified barium swallow or videofluoroscopy are required for its diagnosis. Swallowing therapy may improve swallowing efficiency and reduce the aspiration rate, and should be started immediately. SUMMARY: Successful management of swallowing dysfunction following chemoradiation is a complex undertaking requiring a team approach. Collaboration among different specialists (physicians, speech pathologist, dietitian, and psychologists) remains the key to a desirable outcome.

Quality of life following chemoradiation and postoperative radiation for locally advanced head and neck cancer.

BACKGROUND: To evaluate the impact of chemoradiation and postoperative radiation on patients' quality of life (QOL) in a single institution. METHODS: A retrospective analysis of 101 patients who had treatment for locally advanced head and neck cancer in a single institution. Forty-seven patients had chemotherapy and radiation, 54 patients underwent postoperative radiation. QOL was assessed with the University of Washington (UW), and the Hospital Anxiety (HA) and Depression (HD) questionnaires. All patients were free of disease at the survey time. RESULTS: Mean and median UW scores were not different between the 2 groups: chemoradiation (65/67), postoperative radiation (62/63). Mean and median HA scores were 7.6/7 (chemoradiation), and 8.3/8 (postoperative radiation). Mean and median HD scores were 6.7/7 (chemoradiation), and 7.1/7 (postoperative radiation). Forty-four patients developed complications, with mean/median UW, HA, and HD scores of 55/55, 9.9/8, and 8.9/9, respectively. These scores were significantly different compared to the 57 patients without complications: 70/70 (p = 0.0001), 6.5/6 (p = 0.001), and 8.9/9 (p = 0.0001). CONCLUSION: There was no significant difference in QOL between chemoradiation and postoperative radiation in this retrospective study with a relatively short follow-up in the chemoradiation group. In addition, there were more patients with resectable disease in the postoperative group which may explain the lack of difference in QOL between the two groups. Patients who developed complications following treatment experienced lower QOL, more anxiety and depression. Our study raised the need to conduct a prospective randomized study to assess the real impact of chemoradiation and postoperative radiation on patients' QOL.

Aspiration rate following chemoradiation for head and neck cancer: an underreported occurrence.

BACKGROUND AND PURPOSE: We would like to assess the prevalence of aspiration before and following chemoradiation for head and neck cancer. PATIENTS AND METHODS: We reviewed retrospectively the Modified Barium Swallow (MBS) in 63 patients who underwent concurrent chemotherapy and radiation for head and neck cancer. MBS was performed prior to treatment to determine the need for immediate gastrostomy tube placement. MBS was repeated following treatment to assess the safety of oral feeding prior to removal of tube feeding. All patients were cancer free at the time of the swallowing study. No patient had surgery. Dysphagia severity was graded on a scale of 1-7. Tube feedings were continued if patients were diagnosed to have severe aspiration (grade 6-7) or continued weight loss. Patients with abnormal swallow (grade 3-7) received swallowing therapy following MBS. RESULTS: Before treatment, there were 18 grade 1, 18 grade 2, 9 grade 3, 8 grade 4, 3 grade 5, 3 grade 6, and 4 grade 7. Following chemoradiation, at a median follow-up of 2 months (1-10 months), one patient had grade 1, eight patients had grade 2, nine patients had grade 3, eight patients had grade 4, 13 patients had grade 5, seven patients had grade 6, and 11 patients had grade 7. Six patients died from aspiration pneumonia (one before, three during, and two post-treatment), and did not have the second MBS. Overall, 37/63 (59%) patients developed aspiration, six of them (9%) fatal. If we excluded the 10 patients who had severe aspiration at diagnosis and the six patients who died from pneumonia, the prevalence of severe aspiration was 33% (21/63). CONCLUSIONS: Aspiration remained a significant morbidity following chemoradiation for head and neck cancer. Its prevalence is underreported in the literature because of its often silent nature. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, and for rehabilitation.

Safety and effectiveness of prophylactic gastrostomy tubes for head and neck cancer patients undergoing chemoradiation.

BACKGROUND: We would like to assess the safety and effectiveness of prophylactic percutaneous endoscopic gastrostomy (PEG) tube feedings during concurrent chemoradiation for head and neck cancer. METHODS: Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. All patients underwent PEG tube placement prior to the treatment because of the expected mucositis. Gastrostomy tubes were removed following treatment when the patients were able to resume oral feedings without aspiration. RESULTS: Between March 1999 and 2006, 104 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. One patient declined placement of gastrostomy tube. Ninety patients (86%) developed grade 3-4 mucositis during chemoradiation. Five patients died during treatment from aspiration pneumonia and sepsis. One hundred two patients lost weight during treatment. The mean and median weight loss during concurrent therapy was, respectively, 8.5 and 8 kg (1-23.5 kg). Following treatment, tube feedings were continued 1-41 months (mean: 8 months; median: 5 months) because of continued weight loss, chronic dysphagia, or aspiration. At a median follow-up of 19 months (1-62 months), no patient developed serious complications from tube feedings. CONCLUSION: Dysphagia resulting from the severe mucositis produced severe weight loss, despite tube feedings. Gastrostomy tube feedings are safe. Gastrostomy tubes should be placed prophylactically for patients undergoing chemoradiation for head and neck cancer.

Evolution of chronic dysphagia following treatment for head and neck cancer.

We would like to assess the evolution of chronic dysphagia (1 year or more) following treatment for head and neck cancer. Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1-7. Each patient had at least 2 MBS. Severity of dysphagia was compared between the first and last MBS study to determine whether the swallowing dysfunction had returned to normal. Patients with complaint of dysphagia and normal MBS also underwent a regular barium swallow to assess the structural integrity of the pharynx and esophagus. Between 1996 and 2001, 25 patients with dysphagia underwent repeat MBS following treatment. Swallowing dysfunction did not return to normal in the majority of the patients. At a median time of 26 months following treatment (range 15-82 months), only two patient (8%) had normalization of the swallowing. The severity of dysphagia decreased in eight patients (32%), remained unchanged in 12 patients (48%), and worsened in five patients (20%). Eight patients (32%) still had aspiration problems at 12-83 months following treatment. Six patients (24%) required dilation because of pharyngeal stenosis. Three patients who required dilation had improvement of the dysphagia severity. Chronic dysphagia is a relentless process possibly due to excessive scarring. Patients with chronic dysphagia are at risk of malnutrition, and aspiration. Management of chronic dysphagia requires a team approach with nutritional support, psychological counseling, dilation, and tube feedings when indicated.

Dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer.

OBJECTIVE: The purpose of the study is to evaluate dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer, and particularly the aspiration risk because of its potential life-threatening consequence. MATERIALS AND METHODS: We reviewed retrospectively the modified barium swallow (MBS) results in 110 patients who complained of dysphagia following chemoradiation (57) and postoperative radiation (53) of their head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1-7. Patients were grouped according to the dysphagia severity: mild (grades 2-3), moderate (grades 4-5), and severe (grades 6-7). RESULTS: Mean and median dysphagia grades were 4.84/5 and 4.12/4 for chemoradiation and postoperative radiation respectively. The mean difference between the two groups is statistically significant (p=0.02). Mild dysphagia occurred in 13 patients (22%) of the chemoradiation group and 17 (32%) of the postoperative group. Corresponding number for the moderate group was 25 (43%) and 25 (48%), respectively. Severe dysphagia was significant in the chemoradiation group (34%) compared to the postoperative group (19%). However, the difference was not statistically significant (p=0.29). There was a higher proportion of patients with large tumor (T3-T4) in the chemoradiation group who developed severe dysphagia. CONCLUSION: Dysphagia remained a significant morbidity of chemoradiation and postoperative radiation for head and neck cancer. Dysphagia may be more severe in the chemoradiation group because of the higher proportion of patients with large tumor, the high radiation dose, and a high number of oropharyngeal tumors. Aspiration occurred in both groups. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, as it may be silent.

Impact of dysphagia on quality of life after treatment of head-and-neck cancer.

PURPOSE: To evaluate the quality of life (QOL) associated with dysphagia after head-and-neck cancer treatment. METHODS AND MATERIALS: Of a total population of 104, a retrospective analysis of 73 patients who complained of dysphagia after primary radiotherapy (RT), chemoradiotherapy, and postoperative RT for head-and-neck malignancies were evaluated. All patients underwent a modified barium swallow examination to assess the severity of dysphagia, graded on a scale of 1-7. QOL was evaluated by the University of Washington (UW) and Hospital Anxiety and Depression questionnaires. The QOL scores obtained were compared with those from the 31 patients who were free of dysphagia after treatment. The QOL scores were also graded according to the dysphagia severity. RESULTS: The UW and Hospital Anxiety and Depression scores were reduced and elevated, respectively, in the dysphagia group compared with the no dysphagia group (p = 0.0005). The UW scores were also substantially lower among patients with moderate-to-severe (Grade 4-7) compared with no or mild (Grade 2-3) dysphagia (p = 0.0005). The corresponding Hospital Anxiety (p = 0.005) and Depression (p = 0.0001) scores were also greater for the moderate-to-severe group. The UW QOL subscale scores showed a statistically significant decrease for swallowing (p = 0.00005), speech (p = 0.0005), recreation/entertainment (p = 0.0005), disfigurement (p = 0.0006), activity (p = 0.005), eating (p = 0.002), shoulder disability (p = 0.006), and pain (p = 0.004). CONCLUSION: Dysphagia is a significant morbidity of head-and-neck cancer treatment, and the severity of dysphagia correlated with a compromised QOL, anxiety, and depression. Patients with moderate-to-severe dysphagia require a team approach involving nutritional support, physical therapy, speech rehabilitation, pain management, and psychological counseling.

Chronic disseminated candidiasis in patients with acute leukemia: emphasis on diagnostic definition and treatment.

BACKGROUND: Chronic disseminated candidiasis (CDC) is a form of invasive fungal infection that occurs most commonly in patients with acute leukemia treated with chemotherapy. Recent studies have provided evidence for diagnostic alternatives to invasive procedures and more therapeutic options for the management of this complication. In order to put diagnostic criteria and methodological approach to the disease into the perspective of developing strategies for therapy, all relevant studies published in the English literature over the last 30 years were examined. MATERIALS AND METHODS: The English-language articles located through MEDLINE (1966 to present) and from selected bibliographies. RESULTS: There is increased recognition of CDC as complication of treatment with chemotherapy in patients with acute leukemia. Liver biopsy may not always be revealing or feasible to perform in some patients. Among the imaging modalities, magnetic resonance imaging has obtained preeminence as a non-invasive tool for the diagnosis of hepatosplenic fungal infections. Administration of amphotericin B (Amp B) in relatively large cumulative doses is needed to ensure appropriate control of the infection and prevention of future relapse. Patients intolerant of, or refractory to conventional Amp B have been successfully salvaged using fluconazole or lipid formulations of Amp B. A constellation of clinical, laboratory and radiologic parameters should be used to determine response and efficacy of therapy. There is sufficient evidence to support the safety and feasibility of continuing chemotherapy for acute leukemia in conjunction with antifungal treatment in patients diagnosed with CDC. CONCLUSION: The development of CDC in patients with acute leukemia does not preclude further chemotherapy or constitute contraindication for bone marrow transplantation. Knowledge of the course and pattern of evolution of the disease and adopting aggressive therapeutic approach will likely reduce the morbidity and mortality from this complication.

Severity and duration of chronic dysphagia following treatment for head and neck cancer.

UNLABELLED: The purpose of this investigation was to evaluate chronic dysphagia (lasting 3 or more months) following treatment for head and neck cancer. Since dysphagia is a common sequela post therapy in cancer survivors, it may be helpful for the clinician to be aware of the persistence of dysphagia as well as its usual severity. Modified Barium Swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1 to 7. Each patient had sequential MBS and underwent swallowing therapy in between. The severity of dysphagia was compared between the first and last MBS study to determine whether the swallowing function had returned to normal. RESULTS: Between 1996 and 2004, 12 patients with dysphagia underwent repeated MBS following treatment. Swallowing function did not return to normal in all patients. At a median time of 29 months following treatment (range 8 to 94 months), the severity of dysphagia decreased in 8 patients (67%), remained unchanged in 3 patients (25%) and worsened in 1 patient (8%). Chronic dysphagia following treatment is unlikely to resolve with time despite rehabilitation therapy. Excessive scarring following treatment may be responsible for the persistence and severity of dysphagia. Physicians should be aware of the long-term effects of dysphagia on patient nutrition and psychological well-being.

Plasma coagulation markers in patients with solid tumors and venous thromboembolic disease receiving oral anticoagulation therapy.

PURPOSE: To correlate the concentration of plasma coagulation markers at baseline and during follow-up in patients with solid tumors and venous thromboembolic disease with the risk of recurrence and death. EXPERIMENTAL DESIGN: Patients (N = 223) with first episode of venous thromboembolic disease received oral anticoagulation with warfarin for a target international normalized ratio of 2 to 3. Plasma coagulation markers were measured before instituting warfarin and at 3 monthly intervals, thereafter. RESULTS: The median duration of oral anticoagulation was 6.7 months (range 2 weeks to 11 months). Major bleeding episodes occurred in 18 patients (8%), and minor hemorrhagic events occurred in 15 (6.7%) patients. Patients with advanced malignancy (P = 0.032), history of surgery (P = 0.057), and those with poor performance status (P = 0.001) were more likely to encounter major bleeding episodes. Recurrence of venous thromboembolic disease was diagnosed in 31 patients (14%). At univariate analysis, advanced stage of cancer (P = 0.03), performance status > 1 (P = 0.001), treatment with chemotherapy (P = 0.01), the presence of metastatic liver disease (P = 0.03), higher d-dimer (P = 0.001), and thrombin antithrombin complex levels (P = 0.01) were features predictive of recurrent venous thromboembolic disease. At multivariate analysis, poor performance status (P = 0.01) and d-dimer levels (P = 0.001) were predictors of recurrent venous thromboembolic disease. Persistent activation of coagulation as indicated by an upward trend in d-dimer (P = 0.001) and antithrombin (P = 0.001) was observed in patients who developed recurrent thrombosis. Similar upward trends in d-dimer (P = 0.001), antithrombin (P = 0.001), and prothrombin fragment F1 + 2 (P = 0.001) was observed in the 76 patients who died during the study period and in the patients who received chemotherapy. CONCLUSIONS: Successful oral anticoagulation with warfarin in patients with cancer and venous thromboembolic disease is more likely to be achieved in patients with early stage tumors and good performance status. The persistence of activation of hemostasis as shown by plasma coagulation markers is a strong predictor of recurrence and poor outcome.

Venous thrombosis in patients with solid tumors: determination of frequency and characteristics.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are well recognized complications of cancer. However, our current knowledge of this association is derived from studies conducted more than a decade ago. In light of the changes in medical practice and the improvement in cancer care in recent years, a re-evaluation of the relationship between malignancy and venous thrombosis is in order. Of a total of 1041 patients with solid tumors admitted to 3 major medical centers, there were 81 (7.8%) diagnosed with DVT/PE. Patients were more likely to develop DVT/PE during chemotherapy (p = .0001). Advanced malignancies (p = .001), renal carcinoma (p = .005), pancreatic (p = .001), gastric (p = .014) and brain tumors (p = .001) were independent variables strongly associated with the occurrence of venous thrombosis. The occurrence of thrombotic events in the population tested in this study did not adversely affect survival (p = .082). The study identifies subset of patients with cancer at high risk for venous thrombosis. Early prophylaxis with anticoagulants in these patients may be warranted. Most importantly, further clinical trials are desperately awaited to detect possible new trends in the frequency and types of thrombotic events and to better define prevention strategies in cancer patients at risk for thrombosis. The association between venous thromboembolic disease (VTD) and malignant neoplastic disorders is well known and has been the subject of several reports for more than a century. There is a general agreement among investigators that thrombotic complications in patients with cancer occur at a rather high frequency, and that other circumstantial factors such as surgery or chemotherapy potentiates this risk. However, several important considerations pertaining to cancer and thrombosis continue to be shrouded in controversy. For example, there are inexplicable differences in the proportion of patients with cancer diagnosed with deep venous thrombosis (DVT) or pulmonary embolism (PE) reported in the literature. In the absence of large well-controlled studies, one may only postulate on the reasons that contributed to these differences. The inclusion of different types of VTD such as superficial, venous, arterial or vascular access device-induced thrombosis may have led to overestimation of the incidence of these events in patients with underlying malignancy. Another possible explanation for this discrepancy relates to the use of a variety of diagnostic and methodological criteria ranging from observation and clinical suspicion to more invasive procedures resulting in considerable differences in the rate of reported clotting events. Along the same line of discussion, one may argue whether VTD is a random event or constitutes a complication that occurs more commonly in patients with distinct characteristics and certain tumor types. To further investigate the association between malignancy and thrombosis, we evaluated 1041 patients with solid tumors for the risk of DVT/PE. The main objectives of the study were to determine the frequency of DVT/PE based on validated diagnostic criteria and to identify patients with cancer at high risk for developing these thrombotic episodes. Also, we evaluated the impact of VTD on the survival of these patients.

Erythropoietin modulates the anticancer activity of chemotherapeutic drugs in a murine lung cancer model.

In this study, we assessed the ability of erythropoietin (EPO) to synergize with various chemotherapeutic agents and suppress the growth and metastasis of solid tumors. Animals were inoculated with Lewis lung carcinoma (LLC) cells and treated with EPO alone, the designated chemotherapeutic drug (cisplatin, mitomycin C or cyclophoshamide) alone, or EPO and the drug. Tumor volume was monitored daily. Thirteen days following cell injection, tumor mass was determined. In addition, the number of the metastatic foci in the lungs was determined. Cisplatin alone was capable of inducing a 7-fold decrease in final tumor volume compared to tumor-bearing animals injected with saline. However, when EPO was combined with cisplatin, the animals experienced an 11-fold reduction in final tumor volume compared to saline-injected animals (P<0.001). A 2.5-fold reduction in tumor mass was observed in animals treated with cisplatin, compared to the saline-injected groups. Furthermore, injections of EPO and cisplatin induced a 4-fold reduction in tumor mass (P<0.001). Blood analysis indicated that a significant increase of more than 30% in WBC was found in animals injected concurrently with cisplatin and EPO, as compared to saline-injected mice (P<0.03). When EPO and mitomycin C were injected together, tumor mass was further reduced by 14% compared to that seen in mice treated with mitomycin C alone. However, this difference was not statistically significant. We conclude from this study that EPO can synergize with chemotherapeutic agents to further suppress the growth of tumors. The level of synergism is drug related.

Amifostine and curative intent chemoradiation for compromised cancer patients.

Concurrent chemotherapy and radiation are usually indicated for locally advanced carcinomas such as head and neck and anal malignancies. Because of the toxicity of the treatment, patient selection plays an important role in recommendations to treat with a curative intent. Elderly patients (> 70 years), those with underlying medical conditions or acquired immunological disorders (AIDS) are commonly excluded from combined modality therapy because of their perceived inability to tolerate the aggressive treatment. They may thus be deprived of a potentially curative therapy. In an attempt to improve outcome, we conducted a pilot study using amifostine, a radioprotector, to increase the tolerance of such compromised individuals to treatment. Amifostine (500 mg intravenously) was given during chemotherapy on days 1-5, and days 21-25 of radiation regimen. All patients were able to complete the chemoradiation. Despite the locally advanced stage of the disease, five out of our six patients achieved a complete response (CR). One patient with synchronous primaries had a complete response for the base of tongue cancer and regression of the esophageal cancer, which allowed him to resume oral feeding. All patients achieved improved quality of life. Successful chemoradiation appears to be feasible in patients with advanced stage, age and/or underlying medical conditions when amifostine is integrated in the treatment.

Efficacy of combined radiation, paclitaxel and carboplatin for locally advanced non-small cell lung carcinoma.

Locally advanced non-small cell lung carcinoma (NSCLC) has a poor prognosis when treated with conventional chemotherapy and radiation. New chemotherapy agents like paclitaxel may increase the sensitivity of tumors cells to radiation and potentially improve the outcome. The optimal combination of taxane-based chemotherapy agents and radiation is still unclear. We investigated the feasibility of induction chemotherapy followed by concurrent near systemic dose of chemotherapy with radiation. A prospective survey of 29 previously untreated patients with unresectable stage III (15 IIIA, 14 IIIB) NSCLC treated with paclitaxel and carboplatin in combination with radiation was reviewed. The patients received 2 cycles of paclitaxel 225 mg/m2 intravenously (i.v.) over 3 hours, days 1, 22; carboplatin at area under the curve (AUC) 6 based on Calvert formula days 1, 22 following completion of the paclitaxel infusion. Following induction chemotherapy, radiation therapy started on day 43 until completion to a tumor dose of at least 5960 cGy. Cycles 3 and 4 of chemotherapy were begun on days 43 and 63, respectively, and consisted of paclitaxel 175 mg/m2 i.v. over 3 hours, and carboplatin at AUC 6 following paclitaxel infusion. The response rate, acute toxicity, long-term complications, pattern of failure and survival were evaluated and compared to previous studies in the literature. Two patients were lost to follow-up. The response rate to induction carboplatin/paclitaxel was 52%. An overall response rate (complete and partial responders) of 85% was obtained following chemotherapy and radiation. Grade 3-4 acute side-effects were recorded in 9 patients (31%) and consisted of esophagitis (8 patients) and anemia (1 patient). One patient died from cachexia 3 months following treatment (3.7%). The median survival and 3-year survival were 15 months and 30%, respectively, for the remaining 27 patients at a median follow-up of 11 months. There was no difference in survival between stages IIIA and IIIB at 2 years (IIIA: 22%, IIIB: 31%). Local or regional recurrences and distant metastases developed in 9 patients (33%) and 13 patients (46%), respectively. The combination of paclitaxel, carboplatin and radiation for locally advanced non-small cell carcinoma is feasible with acceptable toxicity. The response rate compares favorably with previously reported studies. The decrease of tumor volume following induction chemotherapy allows sparing of the lungs from the toxicity of radiation. However, grades 3-4 esophagitis remain significant. The addition of amifostine may be beneficial in this setting.

Recombinant activated factor VII in patients with cancer and hemorrhagic disseminated intravascular coagulation.

Hemorrhagic disseminated intravascular coagulation (DIC) associated with the presence of underlying advanced or metastatic tumors are often difficult to control by conventional methods. We report the use of recombinant activated factor VII (rFVIIa) in patients with cancer and bleeding secondary to DIC. A total of 18 patients with cancer met pre-defined criteria for DIC. All patients had failed to respond to transfusion with blood products and treatment of the underlying malignancy prior to the introduction of rFVIIa. The median laboratory data at the time of treatment with rFVIIa were as follows: hemoglobin, 7.7 g/dl; platelets, 54 x 10(9)/l; prothrombin time, 21 s; activated partial thromboplastin time, 41 s fibrinogen, 83 mg/dl; D-dimer, 17 microg/ml; and antithrombin, 32%. The dose of rFVIIa was 90 microg/kg and the median number of doses administered was 5 (range, 3-10). Serial measurements of coagulation parameters were obtained at frequent intervals during treatment with rFVIIa. Of the 18 patients, 15 responded with cessation of bleeding and improvement in coagulation data. The prothrombin time and activated partial thromboplastin time normalized in all responding patients within 24 h of treatment. The median fibrinogen was 214 mg/dl while the median D-dimer was 6 microg/dl at 48 h following the administration of rFVIIa. No thromboembolic complications were observed following rFVIIa. Our data provide evidence that rFVIIa can be used successfully to control the hemorrhagic episodes associated with DIC. Although this type of treatment appears to be safe, close monitoring of the patients is warranted.