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Biomedical subjects

S G Urba

Publications and source records attributed to S G Urba.

16 recordsLinked to original sources
PubMed2001

Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma.

PURPOSE: A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution. We designed a randomized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone. MATERIALS AND METHODS: One hundred patients with esophageal carcinoma were randomized to receive either surgery alone (arm I) or preoperative chemoradiation (arm II) with cisplatin 20 mg/m2/d on days 1 through 5 and 17 through 21, fluorouracil 300 mg/m2/d on days 1 through 21, and vinblastine 1 mg/m2/d on days 1 through 4 and 17 through 20. Radiotherapy consisted of 1.5-Gy fractions twice daily, Monday through Friday over 21 days, to a total dose of 45 Gy. Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42. RESULTS: At median follow-up of 8.2 years, there is no significant difference in survival between the treatment arms. Median survival is 17.6 months in arm I and 16.9 months in arm II. Survival at 3 years was 16% in arm I and 30% in arm II (P = .15). This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years, with at least 80% power. CONCLUSION: This randomized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference.

Adenocarcinoma↗
PubMed2000

Neoadjuvant therapy for organ preservation in head and neck cancer.

OBJECTIVES/HYPOTHESIS: We designed two sequential trials of induction chemotherapy followed by definitive radiation in patients with potentially resectable head and neck cancer to determine whether organ preservation is feasible without apparent compromise of survival Study Design Both trials were Phase II studies. METHODS: Two clinical trials were conducted sequentially at the University of Michigan. Fifty-two patients enrolled in the first study and were treated with a planned three cycles of carboplatin and 5-fluorouracil. Patients who achieved at least 50% reduction in the size of the primary tumor received definitive radiation therapy, to a dose of 6600 to 7380 cGy. Patients with minimal response or progression had immediate salvage surgery. Thirty-seven patients enrolled in the second trial, in which the chemotherapy consisted of carboplatin, 5-fluororuracil, and leukovorin. Responders were treated with accelerated radiation therapy, to a total dose of 7120 cGy delivered in 41 fractions over 5.5 weeks. RESULTS: Toxicity and response were similar in both trials; therefore, the results are reported first separately and then combined for all 89 patients. Tumor sites included: oropharynx, 55 patients; hypopharynx, 34 patients. Eighty-three percent of patients tolerated all three cycles of chemotherapy and toxicity was mild. Response to chemotherapy was: 48% complete response at the primary tumor site, and 34% partial response at the primary tumor site. Initial organ preservation at individual tumor sites was: oropharynx, 58%; hypopharynx, 59%. Median survival was 28 months, and survival at 3 and 5 years was 40% and 24%, respectively. CONCLUSIONS: These two regimens were well tolerated, and survival did not appear to be compromised by organ preservation treatment compared with historical controls. This approach warrants further investigation, particularly in those patients for whom surgery could be functionally debilitating.

Adult↗
PubMed1999

Concurrent chemoradiotherapy in head and neck cancer.

Historically, patients with unresectable head and neck cancer have been treated with definitive radiation therapy alone. In recent years, numerous trials have assessed the role of concurrent chemoradiation for these patients. Many of the larger, more recent trials are summarized here, with particular emphasis on the effect of combined therapy on survival and toxicity. Most of the trials have demonstrated modest benefit or a trend toward benefit in survival, progression-free survival, or local control in patients treated with concurrent chemoradiation. However, nearly every trial also showed increased toxicity with the more aggressive regimens. Two meta-analyses also show a small but significant improvement in survival and increased toxicity from a concurrent treatment approach. Therefore, patients should be well selected by their physicians to be able to tolerate the side effects of combined-modality therapy and must be well informed of the pros and cons of concurrent chemoradiation during the decision-making process.

Antineoplastic Agents↗
PubMed1999

Chemotherapy in head and neck cancer. Overview of newer agents.

Several new chemotherapy agents show varying degrees of activity in head and neck cancer. The most extensively studied and most promising agents at this time are the taxanes, particularly paclitaxel. Its exact role in combination with other chemotherapeutic agents or with radiation is still being clarified in clinical testing, but it is certainly reasonable to use paclitaxel for palliation of metastatic or recurrent disease. Docetaxel is a more recently developed agent, and more information regarding its use in palliative therapy will be forthcoming as results from the international randomized trial become available. Gemcitabine has shown very modest activity when used as a single agent or in combination therapy, although further data from ongoing research have not yet been reported. It is an extraordinarily potent radiosensitizer in the head and neck, but unfortunately it appears to have a very narrow therapeutic ratio and should certainly not be used with radiation outside of a clinical trial with careful monitoring of toxicity. Topotecan does not appear to be a clinically useful single agent in treating head and neck cancer, and vinorelbine has shown minimal activity in the few clinical trials that have been conducted in head and neck cancer. Nedaplatin is a very new drug, and it is not possible to draw conclusions regarding its effectiveness until further evaluation has been completed. Continued investigation of new chemotherapeutic agents in head and neck cancer is needed.

Antineoplastic Agents↗
PubMed1996

Nonpharmacologic pain management in terminal care.

The elderly, terminally ill patient often experiences physical, emotional, and spiritual pain. While pharmacology remains the cornerstone of pain management, non-pharmacologic methods can serve as adjuncts for pain relief, and also serve to enhance the overall quality of the patient's life. Neurostimulation, such as TENS unit, acupuncture, and massage, are based on the gate theory of pain control. These treatments can be useful particularly in muscular pain. Methods aimed at altering the patient's behavior or mood, such as imagery and aromatherapy, can provide an atmosphere of relaxation and comfort. For those patients with localized, particularly difficult to manage areas of pain, specialized neurolytic or neurosurgical methods are available. It would behoove health care practitioners who deal with pain management in elderly, dying patients to add some of these non-pharmacologic methods to their armamentarium of therapies.

Acupuncture Therapy↗
PubMed1995

Split-course accelerated radiation therapy combined with carboplatin and 5-fluorouracil for palliation of metastatic or unresectable carcinoma of the esophagus.

BACKGROUND: Patients with metastatic or unresectable carcinoma of the esophagus have poor survival, but often require palliation of dysphagia. METHODS: Twenty-seven patients with unresectable carcinoma of the esophagus were treated with carboplatin, 5-fluorouracil, and split-course accelerated radiation therapy. Seventy-four percent of patients had adenocarcinoma, and 26% had squamous cell carcinoma. RESULTS: The regimen was well tolerated; 25% of the patients had disease improvement after completing therapy, although the majority of these patients had all of their disease within the radiation field. Ninety-three percent (13/14) of the patients who experienced disease progression during therapy progressed in areas treated with chemotherapy alone. Median survival was 6 months. Fifty-nine percent of the 17 patients who presented with dysphagia achieved durable relief of that symptom. CONCLUSIONS: Carboplatin and 5-fluorouracil have low activity in patients with metastatic esophageal cancer. However, in combination with radiation therapy, this regimen is tolerable when the primary goal is palliation of dysphagia near the end of life. Future studies should focus on identifying more active regimens with response and survival as endpoints.

Adenocarcinoma↗
PubMed1995

Single-agent paclitaxel and paclitaxel plus ifosfamide in the treatment of head and neck cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and ifosfamide both have activity when evaluated as single agents in patients with advanced squamous cell carcinoma of the head and neck. The Eastern Cooperative Oncology Group completed the first phase II trial of paclitaxel in this population, observing a 40% response rate. Confirmatory trials are in progress in the United States and Europe. The Eastern Cooperative Oncology Group is currently evaluating high-dose (200 mg/m2) and low-dose (135 mg/m2) paclitaxel in combination with cisplatin to assess dose-response effects, toxicity, and efficacy. In an effort to identify an alternate to the cisplatin/5-fluorouracil regimen, investigators at Johns Hopkins and the University of Michigan are evaluating the combination of paclitaxel/ifosfamide. The regimen is paclitaxel 170 mg/m2 followed by ifosfamide 5 g/m2 divided over 3 days with mesna. Granulocyte colony-stimulating factor is started 24 hours after completion of the ifosfamide infusion. To date, 13 patients with recurrent and metastatic squamous cell carcinoma of the head and neck have been enrolled in the study. Eight patients have had prior chemotherapy as part of initial curative treatment or for recurrent disease. The best response observed in II evaluable patients is five partial responses, five stable diseases, and one disease progression. On progression, patients who have not been treated with cisplatin/5-fluorouracil receive that combination as second-line therapy. The occurrence of severe, life-threatening toxicity, primarily myelosuppression, has caused this study to be terminated. However, the responses observed have prompted an evaluation of the reverse sequence (ifosfamide followed by paclitaxel), which is now accruing patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Intensive induction chemotherapy and radiation for organ preservation in patients with advanced resectable head and neck carcinoma.

PURPOSE: We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the head and neck. The regimen consisted of intensive chemotherapy followed by radiation therapy alone for patients with good response to treatment. The end points of the study were response rate, organ preservation, toxicity, and survival. PATIENTS AND METHODS: Forty-two eligible patients with carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, and paranasal sinuses were enrolled. Induction chemotherapy consisted of three cycles of mitoguazone, fluorouracil (5-FU), and high-dose continuous infusion cisplatin. Patients who had a complete response to chemotherapy, or whose tumor was downstaged to T1N1, were treated with definitive radiation therapy, to a total dose of 66 to 73.8 Gy. Patients with residual disease greater than T1N1 underwent surgery and postoperative radiation. RESULTS: The overall response rate to chemotherapy was 84%, with a 43% complete response rate, and a 68% complete response rate at the primary tumor site. Sixty-nine percent of patients (29 of 42) were initially spared surgery to the primary tumor site, and four of these patients (14%) required neck dissection only, after radiation therapy. These tumor sites included oral cavity, oropharynx, hypopharynx, larynx, and sinuses. Eventually, five of these patients (17%) required salvage surgery and eight patients (28%) had unresectable or metastatic relapses. With a median follow-up duration of 38.5 months, 36% of all patients have had preservation of the primary tumor site and remain disease-free. The median survival duration is 26.8 months. Toxicity was substantial, with a 70% incidence of grade 3 to 4 granulocytopenia and two septic deaths. CONCLUSION: Organ preservation without apparent compromise of survival was achieved in patients with selected nonlaryngeal sites of head and neck carcinoma. Larger site-specific trials with less toxic regimens conducted in randomized fashion are required to extend these data.

Adenocarcinoma↗
PubMed1993

Intensive recombinant interleukin-2 and alpha-interferon therapy in patients with advanced head and neck squamous carcinoma.

BACKGROUND: Cellular immune deficiency is a consistent finding in patients with advanced head and neck cancer. Interleukin-2 and alpha-interferon are modulators of the immune system. METHODS: Eleven patients with recurrent head and neck cancer were treated in a Phase II study of recombinant human interleukin-2 (rIL-2) and alpha-2a-interferon (Roferon-A, Hoffmann-La Roche, Inc., Nutley, NJ). Each course consisted of rIL-2, 3 x 10(6) U/m2/day, as a continuous intravenous infusion over 24 hours for 4 days, and recombinant alpha-2a-interferon, 5 x 10(6) U/m2/day intramuscularly or subcutaneously daily for 4 days. This treatment was repeated weekly for 4 weeks, and then a second cycle was given after a 2-week break. RESULTS: Two patients (18%) achieved a partial response. Toxic effects were substantial. Three of 11 patients experienced Grade 3 hypotension, 3 patients had Grade 3 oliguria, and Grade 3 fatigue was one of the most common reasons for withdrawal from the study. There were no deaths or need for intensive care monitoring. CONCLUSIONS: In view of the 18% response rate, additional investigation of biologic therapy in advanced head and neck cancer is warranted.

Adult↗
PubMed1993

Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report.

PURPOSE: In 1990 we published the results of an intensive 3-week preoperative chemoradiation regimen for locoregional esophageal cancer that suggested improved survival compared with historical controls. We now report the long-term results at a median follow-up of 78.7 months. PATIENTS AND METHODS: Forty-three patients with locoregional squamous cell carcinoma or adenocarcinoma of the esophagus or cardia were treated with fluorouracil (5-FU), cisplatin, and bolus vinblastine concurrent with radiation administered over 21 days. Transhiatal esophagectomy was performed on day 42. RESULTS: Forty-one patients (95%) completed the preoperative treatment, and 36 (84%) had a potentially curative resection. Ten of 41 (24%) had no tumor in the resected esophagus and nodal tissues (path-negative group). The median survival duration of all 43 patients registered on study was 29 months; 34% were alive at 5 years. By histology, median survival durations were 32 months for 21 adenocarcinoma patients and 23 months for 22 squamous cell patients, with corresponding 5-year survival rates of 34% and 31%, respectively. Analysis of the 36 patients who underwent a potentially curative resection demonstrated median survival durations of 32 and 44 months and 5-year survival rates of 36% and 43%, respectively, for adenocarcinoma and squamous cell histologies. Path-negative (complete response [CR]) patients had a median survival duration of 70 months and 60% were alive at 5 years, while those patients with residual tumor in the resected esophagus had a median survival duration of 26 months and 32% were alive at 5 years (P = .114 by the log-rank test and P = .04 by the Wilcoxon test). CONCLUSION: The results of this regimen appear improved over those reported with surgery alone, with an approximate doubling of the 5-year survival rate. Thirty-two percent of patients with residual tumor in the esophageal specimen are long-term survivors, which suggests a benefit from esophagectomy. A randomized trial is in progress to compare this preoperative regimen with immediate surgery.

Adenocarcinoma↗
PubMed1992

Concurrent preoperative chemotherapy and radiation therapy in localized esophageal adenocarcinoma.

Twenty-four patients with localized, potentially resectable adenocarcinoma of the esophagus were enrolled in this study to evaluate the use of preoperative chemotherapy and radiation therapy, followed by transhiatal esophagectomy. The patients were newly diagnosed and had received no prior treatment. Radiation therapy consisted of 4900 cGy, administered as 350-cGy fractions 5 days a week for 14 fractions. The chemotherapy consisted of 5-fluorouracil 300 mg/m2/day administered as a continuous 24-hour intravenous infusion for 96 hours each week, concomitantly with the radiation therapy. After a 3-week rest, patients underwent transhiatal esophagectomy. Twenty-two patients could be observed for their responses to the chemotherapy and radiation regimen. Radiographically, 41% showed improvement, 36% had stable disease, and 23% had progression. Nineteen patients underwent surgery; all patients had total gross removal of disease, and two patients had a complete histologic response. All 24 patients could be examined for toxicity assessment. There were three deaths during the treatment period: one patient died of a perioperative complication, one of pneumonia, and one of a myocardial infarction. Eleven patients eventually had pleural and/or pericardial effusions, and six of these were symptomatic. All 24 patients could be examined for survival analysis. The median follow-up for all patients was 12.5 months, with 32.5 months for all surviving patients. Median survival was reached at 11 months. Disease-free survival was 9.5 months. It was concluded that the radiation-fractionation schedule in this preoperative regimen was associated with marked toxicity in the form of pleural and pericardial effusions. There was no improvement in survival compared with historic controls. The role of combined preoperative treatment in this patient population has yet to be determined.

Adenocarcinoma↗
PubMed1990

Concurrent chemotherapy and radiation therapy followed by transhiatal esophagectomy for local-regional cancer of the esophagus.

Forty-three patients with local-regional squamous-cell carcinoma of the esophagus or adenocarcinoma of the esophagus, cardia, or gastroesophageal junction were treated with concurrent cisplatin, vinblastine, fluorouracil (5-FU), and radiation therapy (RT) over 21 days. A transhiatal esophagectomy (THE) was planned on day 42. Seventy-nine percent had T2 primaries by clinical staging and 56% had enlarged regional nodes (N) on computed tomographic (CT) scan. Forty-one patients completed the preoperative treatment and went to surgery (95% operability rate), and 36 (84%) were completely resected. Ten of the 41 operative candidates had no evidence of tumor in the resected esophagus and nodal tissue (tumor0 node0; T0N0), 24% complete response (CR). Myelosuppression was the major toxicity with grade 3 or 4 leukopenia in 93% of patients and two preoperative treatment-related deaths. At a median follow-up of 26 months, the median survival time (MST) of all 43 patients registered on study has not been reached. The MST of the 36 completely resected patients and the 10 complete responders has not been reached; 70% and 100%, respectively, are alive at 24 months. The MST by histology is 21 months for the 22 squamous patients and has not been reached for the 21 adenocarcinoma patients registered on study. In a prognostic factor analysis, clinical N status, histology, and the percent of cisplatin and vinblastine tolerated were significant predictors for survival. These survival results suggest a significant improvement over the 14-month MST observed in our previous trial using preoperative chemotherapy only in a similar patient population, and a 12-month MST in a historic control group undergoing THE. A randomized trial is now in progress to convincingly determine if survival is prolonged by this therapy.

Adenocarcinoma↗
PubMed1990

Tamoxifen therapy in patients with recurrent laryngeal squamous carcinoma.

Twelve patients with recurrent, advanced laryngeal carcinoma were treated with tamoxifen hormonal therapy. Rationale was based on previous in vitro data identifying estrogen receptors and progesterone receptors in some laryngeal carcinoma cell lines. Four patients received tamoxifen, 10 to 20 mg by mouth twice a day; eight received 40 mg by mouth four times a day. The drug was well tolerated at all dose levels. There were no clinical responses. Two patients' tumor tissue was assayed for estrogen and progesterone receptors. One was negative for both, and the other was indeterminate for estrogen receptors and negative for progesterone receptors. A review of literature and a discussion of the possible reasons for the negative results are presented.

Aged↗
PubMed1989

Systemic therapy of head and neck cancer: most effective agents, areas of promise.

The management of squamous cell cancer of the head and neck is a challenging problem. However, "induction" chemotherapy administered prior to surgery and radiation therapy in newly diagnosed patients is showing encouraging results for the preservation of organ function and is the focus of multi-institutional trials. Concurrent chemotherapy and radiation therapy is another approach with promise for unresectable disease. Recent studies combining cisplatin with radiation therapy have reported minimal enhancement of mucocutaneous toxicity and promising survival data. Other strategies which are just beginning to receive attention in clinical research trials include adjuvant chemotherapy in the disease-free patient and biologic response modifiers.

Antineoplastic Agents↗
PubMedDate not supplied

Neoadjuvant therapy.

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Antineoplastic Agents↗