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Results for “Combined Modality Therapy”

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PubMed2002

INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy.

PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. PATIENTS AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach, after stratification by weight loss, primary tumor size, and histology, were randomized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil (5-FU) (1,000 mg/m(2)/24 hours for 4 days) and cisplatin (75 mg/m(2) bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive. RESULTS: For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm, seven of the 11 deaths occurred in patients who had received 50.4 Gy or less. CONCLUSION: The higher radiation dose did not increase survival or local/regional control. Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm, it did not seem to be related to the higher radiation dose. The standard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy.

Adenocarcinoma↗

PubMed1982

Chemotherapy and combined modality therapy for Hodgkin's disease: a progress report on Cancer and Leukemia Group B studies.

Between 1974 and 1977, the Cancer and Leukemia Group B (CALGB) initiated four studies which address current major questions in the therapy for Hodgkin's disease. The efficacy of chemotherapy alone as compared with combined modality therapy in patients with poor-prognostic stages I and II is evaluated in CALGB 7751. Currently, both therapies produce very high complete remission rates in asymptomatic patients; the remission rate is better with combined modality therapy in symptomatic patients. Single and combined modality therapies are compared for stage III patients in CALGB 7451. Complete remission rates have been similar, but relapse-free survival is superior for patients treated with local nodal radiotherapy followed by chemotherapy (P = 0.04). In particular, stage IIIA patients with nodular sclerosis seem to benefit from the inclusion of radiotherapy in their initial treatment. In CALGB 7551, the efficacy of chemotherapy alone versus chemotherapy plus radiotherapy to areas of bulky disease is under study in patients with stages IIIB and IV. Currently, a relapse rate of less than 10% has been seen among sites irradiated, and survival is best for patients treated with radiotherapy bracketed by chemotherapy. Finally, the role of two alternating non-cross-resistant combination chemotherapy programs is being studied in CALGB 7552. Relapse-free and overall survival is better with the doxorubicin-containing regimen than with either the alternating or alternate chemotherapy program. At present, the median followup for each of these studies is less than 5 years. Further observation is required to answer the critical questions relating to prolonged disease-free survival and cure.

Adult↗

PubMed1995

Combined modality therapy for gynecologic cancer.

The use of combined modality therapy in the primary management of gynecologic cancer continues to be explored. Although early ovarian cancer is treated with postoperative adjuvant treatment, the data to support its value is lacking. In advanced disease, paclitaxel has emerged as the most optimal treatment after maximal cytoreduction. Although studies on consolidative therapy using radiotherapy, intraperitoneal therapy, or further chemotherapy are reported, there are no comparative data against a control arm. In those subsets of endometrial cancer patients who have a poor survival, adjuvant treatment strategies using chemotherapy or wide-field whole-abdominal therapy is being evaluated to improve outcome. Small phase II studies of either sequential or concurrent chemotherapy with radiation continue to be reported in advanced cervix cancer, yet large prospective randomized trials comparing standard radiotherapy to combined chemotherapy and radiotherapy are scarce. Alternative strategies to standard surgery to limit morbidity is being explored in the management of vulvar cancer with encouraging results. More properly conducted phase III trials are necessary to evaluate the efficacy of these newer treatment strategies.

Clinical Trials as Topic↗

PubMed2004

Combined modality therapy of resectable rectal cancer: current approaches.

There are two conventional treatments for clinically resectable rectal cancer. First is surgery and, if the tumor is in stage T3 or N1-2, this is followed by postoperative combined modality therapy. The second is preoperative combined modality therapy followed by surgery and postoperative combined modality therapy if the tumor is classified at ultrasound as uT3-4 or N+. A number of new chemotherapeutic agents have been developed for the treatment of patients with colorectal cancer. Ongoing phase I and II trials are examining the use of these new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting; early results suggest that the complete response rates are higher. Based on results from phase I and II trials, the standard regimen for patients who receive combined modality therapy is continuous infusion 5-fluorouracil (5-FU) and pelvic radiation. Regimens using CPT-11 or oxaliplatin-based combined modality therapy plus either continuous infusion 5-FU or capecitibine are under active development.

Antineoplastic Agents↗

PubMed1989

Treatment of sarcomas of the chest wall using intensive combined modality therapy.

As part of two sequential protocols using intensive combined modality treatment in pediatric and adolescent sarcomas, 31 consecutive patients with primary chest wall tumors were treated between November 1977 and March 1986. This group included 13 patients with peripheral neuroepithelioma (Askin's tumor), 11 patients with Ewing's sarcoma, 3 patients with rhabdomyosarcoma, and 4 patients with undifferentiated sarcomas. Following complete work-up, 17 patients presented with localized disease and 14 patients presented with metastases. Patients received intensive combined modality treatment with combination chemotherapy (vincristine, cyclophosphamide, Adriamycin, +/- actinomycin-D and DTIC) and high-dose conventionally fractionated radiation therapy to the primary (55-60 Gy) and non-pulmonary metastases (45-50 Gy). Radiation techniques used for the primary chest wall tumor varied with the clinical presentation. Patients achieving a complete response received either low-dose fractionated TBI (1.5 Gy/0.15 Gy fx/5 weeks) or high-dose TBI (8 Gy/4 Gy fx/2 days) and an intensive cycle of chemotherapy followed by autologous bone marrow transplantation. Twenty-five of 31 patients were judged to have a complete response (including 1 patient with complete resection). With minimum follow-up of 6 months and median follow-up of 36 months from completion of treatment, 14 patients remain disease-free with 2 additional patients alive in second remission after relapse. Patients with localized disease at presentation have improved disease-free survival and overall survival compared to patients with metastases at presentation. All 17 localized patients achieved a CR and 11 are NED compared to 8 of 14 metastatic patients achieving a CR and only 3 are NED. There have been 5 loco-regional recurrences with 3 "in-field" failures and 2 failures in the regional pleura. There were no treatment-related deaths and no clinically significant cases of pneumonitis. To date, 2 patients have significant treatment related morbidity, including 1 patient with scoliosis requiring surgery and 1 patient with acute leukemia developing 42 months after the start of therapy (presently in remission). We conclude that this intensive combined modality therapy results in a high CR rate and good local control with acceptable morbidity. Patients with metastatic disease at presentation remain a therapeutic challenge.

Adolescent↗

PubMed2003

Combined modality therapy in the treatment of gynecologic malignancies.

During the last several years, combined modality therapy has become increasingly important in the treatment of several malignancies. This trend holds true in the treatment of the gynecologic malignancies. In this review we examine the evolving role of combined modality therapy in the treatment of patients with cervical, vulvar, endometrial, and ovarian cancers. Definitive combined chemoradiation has become the new standard of care for patients with locally advanced cervical cancer. Combined chemoradiation provides for improvements in many clinical endpoints, including overall and disease-free survival. Chemoradiation has been used with some success in the treatment of patients with locally advanced vulvar carcinoma and has allowed some patients to avoid disfiguring surgery. Combined chemoradiation is being used in the treatment of patients with endometrial cancer who are found to be at high risk of recurrence after hysterectomy. In the setting of ovarian cancer, abdominopelvic radiation, either with or without chemotherapy, has shown some promise in the treatment of patients with minimal residual disease after resection. Combined modality therapy has played an increasingly important role in the treatment of gynecologic malignancies and its role continues to evolve and expand.

Antineoplastic Agents↗

PubMed2003

Primary adenocarcinoma of the anus treated with combined modality therapy.

PURPOSE: The purpose of this study was to determine the local control and survival of patients with adenocarcinoma of the anus who received combined modality therapy as a component of their treatment. METHODS: Thirteen patients with primary anal adenocarcinoma (T1: 1, T2: 4, T3: 3, T4: 5; and N0: 9, N1: 2, N2: 2) were treated between 1989 and 2001 in the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center. Three general treatment approaches were used that were based on physician and patient preference as well as tumor stage. These included preoperative combined modality therapy followed by abdominoperineal resection (n = 5), with four of the five receiving postoperative chemotherapy; local excision followed by postoperative radiation alone or combined modality therapy (n = 5); and abdominoperineal resection followed by postoperative combined modality therapy (n = 3). Two patients received brachytherapy. RESULTS: With a median follow-up of 19 months, the median survival was 26 months, the local failure rate was 37 percent, and the two-year actuarial survival was 62 percent. In the subset of eight patients treated with abdominoperineal resection and preoperative or postoperative radiation or combined modality therapy, local control was 63 percent, and three of eight are without evidence of disease. Of the five patients who underwent a local excision followed by postoperative radiation or combined modality therapy, the local control rate was 60 percent, with one of the local failures salvaged by abdominoperineal resection and one of five patients without evidence of disease. CONCLUSION: Although the experience is limited, our data suggest that the combination of abdominoperineal resection and combined modality therapy is a reasonable approach for this rare tumor.

Adenocarcinoma↗

PubMed2005

Combined modality therapy of gemcitabine and radiation.

The combination of gemcitabine and radiotherapy is a promising combined modality therapy. However, the clinical application of this combination has to be implemented carefully because of an increased toxicity to normal tissues. A body of experimental evidence shows that gemcitabine is a potent radiosensitizer in vitro and in vivo. The observations so far indicate that various mechanisms are responsible for the radiosensitizing effect. Although it is often difficult to transfer experimental data to the clinic, these studies offer the possibility to develop an improved schedule of administration for patient treatment, based on rational evidence in tumor biology. In the current review, the preclinical data that support the use of gemcitabine as a radiosensitizing agent and the clinical trials that have been conducted to date are summarized.

Animals↗

PubMed2004

Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection.

INTRODUCTION: Recent data suggest a favorable prognosis for rectal cancer patients with a pathologic complete response to preoperative combined modality therapy. Prolongation of the interval between preoperative combined modality therapy and surgery (RT-surgery interval) as a means of increasing pathologic complete response rate has not been fully examined. METHODS: One hundred and fifty-five rectal cancer patients undergoing preoperative pelvic external beam radiation therapy and 5-fluorouracil-based chemotherapy followed by rectal resection were identified. All patients had endorectal ultrasound prior to combined modality therapy. Final pathology reports were reviewed for ypT and ypN stage and margin status. Medical records were reviewed for sphincter preservation, operative time, estimated blood loss, hospital stay, and morbidity (overall, anastomotic, and perineal). RESULTS: A pathologic complete response (ypT0N0) occurred in 24 patients (15 percent). Median RT-surgery interval was 44 (range, 15-206) days. A pathologic complete response occurred in 19 percent of patients with an interval >44 days, vs. 12 percent in those with an interval < or =44 days ( P = 0.27). Downstaging by three stages occurred more frequently in the long-interval group (15 percent vs. 6 percent, P = 0.11). The rates of sphincter preservation, positive margins, estimated blood loss, and operative time were not significantly different. Overall morbidity was similar between groups. CONCLUSIONS: Our results demonstrate a trend toward increased pathologic complete response rate and downstaging with increased RT-surgery interval. However, sphincter preservation is not increased. Until prospective analyses are conducted assessing the impact of prolonged RT-surgery interval on long-term outcome, the benefit of a prolonged interval between the completion of preoperative combined modality therapy and surgery remains unclear.

Adult↗

PubMed1991

Keynote address: modulation of normal tissue toxicity by combined modality therapy: considerations for improving the therapeutic gain.

The aim of combined modality treatment schedules is to achieve increased killing in the tumor cell populations without an equivalent increase in normal tissue damage. There is, however, some increased risk of normal tissue toxicity that must be taken into account when assessing the therapeutic potential. An understanding of the mechanisms involved in combined modality therapy, for example, increased radiosensitivity, inhibition or stimulation of cellular proliferation, or independent additive toxicities, should improve the chances of of achieving a therapeutic gain. A review of the literature of normal tissue effects after combined treatment with drugs and radiation has lead to the following general conclusions: a) The sequence and timing of the two agents have a marked influence on the extent of normal tissue damage, with the most damage occurring when simultaneous drug and irradiation are given within a few days of each other; b) Separation of the two modalities can lead to an improved therapeutic gain since tumor effects are less strongly dependent on the interval between drug and X rays; and c) Chemotherapy can markedly alter the time of expression of radiation damage, particularly in slowly dividing normal tissues, where more rapid expression of injury occurs after combined modality therapy. The above concepts and some possible ways for improving the therapeutic gain in future trials are discussed in this review.

Animals↗

PubMed1996

Opportunities with combined modality therapy for selective organ preservation in muscle-invasive bladder cancer.

Combined-modality therapy for organ preservation represents an appropriate alternative to radical surgery in the management of several malignant diseases. The standard therapy for muscle-invasive bladder cancer in the United States has been radical cystectomy. Although the sequelae of radical surgery have been ameliorated somewhat by techniques for the construction of orthotopic bladders, the ideal therapy should both cure the patient of cancer and maintain a functioning natural bladder. Years of experience in Europe and Canada with bladder preservation using radiation therapy are documented. Advances in transurethral surgery technique and in the combination of radiation and chemotherapy have led to safe and effective regimens for patients with bladder cancer. Several recent trials with combined-modality therapy have established this treatment as a viable alternative to radical cystectomy in selected patients.

Brachytherapy↗

PubMed1999

Esophagitis in combined modality therapy for locally advanced non-small cell lung cancer.

Within the last 10 to 15 years, several randomized trials have validated the importance of chemotherapy in the treatment of locally advanced non-small cell lung cancer and have shown that combined modality therapy improves survival compared with radiotherapy alone. Esophagitis appears to be the primary toxicity, with an increased incidence in combined modality trials. Esophagitis is an inflammatory response of the esophageal mucosa. Treatment with chemotherapy or radiotherapy destroys rapidly dividing cells, such as those in the basal epithelial cell layer. Cell death decreases the renewal rate of the basal epithelium, causing mucosal atrophy, ulceration, and initiation of the inflammatory response. Synergy between chemotherapy and radiotherapy may increase the severity and extent of esophagitis observed with combined modality therapy. Based on Radiation Therapy Oncology Group criteria, the incidence of >/=grade 3 esophagitis following radiation therapy alone or combined modality therapy ranges from less than 5% to 53%. Four sequential, multi-institutional phase I or II studies were conducted during the last 5 years to explore the use of paclitaxel in combined modality therapy for patients with non-small cell lung cancer. In the three phase II trials, esophagitis was the main toxicity, with incidences ranging from 17% to 26% using Radiation Therapy Oncology Group criteria. A multivariate analysis identified a statistically significant correlation between esophageal toxicity and both response to therapy and performance status. Other factors, including gender, age, histology, survival, and length of esophagus within the primary and boost radiation field, were not significantly correlated with esophageal toxicity.

Adult↗

PubMed1997

Combined modality therapy of non-small cell lung cancer.

Combined modality therapy of locally advanced non-small cell lung cancer has become a widely used means of treatment with several reports of benefit found in randomized phase III trials. Progress in this area may, however, be less substantive than it appears. Phase III trials routinely take the better part of a decade to initiate, complete, and analyze, and the flood of phase II trials are largely unable to be compared because of a widespread failure to systematically use readily available staging techniques.

Carcinoma, Non-Small-Cell Lung↗

PubMed1982

The decision between single- and combined-modality therapy in Hodgkin's disease.

Using the technique of decision analysis to evaluate data on single-modality and combined-modality therapy in Hodgkin's disease, we have been able to determine which treatment gives the best chance for prolonged disease-free survival in given settings. Both the potential of combined-modality therapy for inducing secondary hematologic malignancies and the rate of salvage with MOPP following relapse after radiotherapy have been studied to observe the effect of different rates of these variables on the therapeutic decision. An analysis of patients with known pathologic stage endorsed the continued use of extended-mantle radiotherapy for Stages IA and IIA disease; under most of the conditions analyzed, combined-modality therapy appeared the best option for Stage IIIA disease. The results for Stages IB and IIB disease showed neither combined-modality therapy nor total nodal irradiation to have a conclusive advantage. We also analyzed management decisions for patients who had not had pathologic staging. For this, probabilities of each pathologic stage were derived from a large patient data base and were incorporated into the decision analysis. The results of this analysis indicated that, despite the mortality of laparotomy, treatment designated according to pathologic stage was more effective than immediate combined-modality therapy for most types of patients. For certain patients in whom the clinical features could be used to predict a high probability of advanced disease, the most effective management was immediate MOPP chemotherapy without staging laparotomy.

Adult↗

PubMed2005

Complications after preoperative combined modality therapy and radical resection of locally advanced rectal cancer: a 14-year experience from a specialty service.

BACKGROUND: Preoperative combined modality therapy followed by total mesorectal excision has emerged as the optimal treatment paradigm for locally advanced rectal cancer (T3 to 4, N1, or both). But its impact on postoperative complications has not been adequately evaluated. Our aims were to evaluate our comprehensive experience and identify factors predictive of complications in this patient population. STUDY DESIGN: The study group consisted of 297 consecutive patients with locally advanced rectal adenocarcinoma treated with preoperative combined modality therapy (radiation: 5,040 cGy; chemotherapy: 5-FU-based) and then operation. Major complications were defined as those requiring medical or surgical treatment. A prospectively collected database was queried to determine the incidence of postoperative complications and associated clinicopathologic factors. RESULTS: Median followup was 43.9 months (range 0.8 to 128.6 months). There were no postoperative mortalities (within 30 days of operation). But there were 145 major complications in 98 patients (33% of study population). The most common complications were small bowel obstruction (n = 32 [11%]) and wound infection (n = 31 [10%]). There were eight anastomotic leaks (4%) and nine pelvic abscesses (4%) in patients treated with low anterior resection (n = 210). Preoperative comorbidity was the only clinicopathologic factor associated with postoperative complications (p = 0.02). Postoperative complications had no significant impact on oncologic outcomes. CONCLUSIONS: Although postoperative mortalities are rare, complications requiring treatment can be anticipated in one-third of patients undergoing preoperative combined modality therapy and total mesorectal excision. A policy of selective fecal diversion after preoperative combined modality therapy and total mesorectal excision for locally advanced rectal cancer can achieve low rates of pelvic sepsis, but may lead to an increased incidence of small bowel obstruction.

Adenocarcinoma↗

PubMed2004

Combined-modality therapy of rectal cancer with irinotecan-based regimens.

There are two conventional treatments for clinically resectable rectal cancer. The first is surgery followed by postoperative combined-modality therapy if the tumor is T3 and/or N1/2. The second, if the tumor is ultrasound T3 or clinical T4, is preoperative combined-modality therapy followed by surgery and postoperative chemotherapy. There are a number of new chemotherapeutic agents that have been developed for the treatment of colorectal cancer. Phase I/II trials are examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting. There is considerable interest in integrating irinotecan (Camptosar) into preoperative combined-modality therapy regimens for rectal cancer. Based on these trials, the recommended regimen for patients who receive irinotecan-based combined-modality therapy is continuous infusion fluorouracil (5-FU), irinotecan, and pelvic radiation. New trials examining preoperative combined-modality therapy regimens substituting capecitabine (Xeloda) for continuous infusion 5-FU are in progress.

Antimetabolites, Antineoplastic↗

PubMed1986

Pulmonary toxicity with combined modality therapy for limited stage small-cell lung cancer.

To assess the pulmonary toxicity of radiation therapy combined with chemotherapy v chemotherapy alone, we reviewed the clinical course of 80 patients with limited stage small-cell lung cancer treated in a randomized prospective trial. Life-threatening pulmonary toxicity, defined as bilateral pulmonary infiltrates extending beyond radiation ports with symptoms requiring hospital admission, developed in 11 patients (28%) receiving combined modality therapy and in two (5%) receiving chemotherapy alone. Eight of these 13 patients died from pulmonary complications with no clinical evidence of tumor in five. Pulmonary toxicity initially presented at a median of 63 days (range, 21 to 150 days) after the start of combined modality therapy and at a median of 217 days after chemotherapy alone. Biopsies obtained in 11 patients with severe toxicity revealed only interstitial fibrosis with no evidence of an infectious agent. Review of pretreatment parameters such as age, performance status, and radiation portal area failed to reveal any significant differences between patients with or without pulmonary complications. However, initial pulmonary function tests (PFTs) revealed a significantly lower vital capacity (P = .03) and forced expiratory volume (FEV/1.0 second) (P = .04) in patients with subsequent pulmonary complications. Pulmonary toxicity was significantly more common with combined modality therapy than with chemotherapy alone (P = .017) and worse than expected with radiotherapy alone. Six- or 12-month PFTs in completely responding patients revealed improvement within the chemotherapy alone group and no clear trend within the combined modality group. For the group treated with radiation therapy and chemotherapy, there was significantly less improvement after 6 or 12 months in the forced vital capacity (P less than .005) and FEV/1.0 second (P less than .005) than observed for the group treated with chemotherapy alone. Despite the increased incidence of pulmonary toxicity, overall survival favored the combined modality arm (P = .07). Enhanced local control and disease-free survival appeared to compensate for the initial increased pulmonary morbidity and mortality in the group with combined modality therapy.

Adult↗

PubMed2002

[The observation of clinical efficacy of combined modality therapy in 58 cases of perennial allergic rhinitis].

OBJECTIVE: To study the effect of combined modality therapy on perennial allergic rhinitis (PAR). METHOD: Fifty-eight cases of PAR received a 4-weeks treatment with combined beclomethasone dipropionate nasal spray (BDP), cetirizine hydrochloride, ethmoidal nerve radiofrequency treatment, and half-dose combined BDP, cetirizine hydrochlonde was used for improving the recurrence symptoms in one year follow-up. RESULT: The overall effective (excellent/good) rate was 94.83% (excellent 72.41%, good 22.41%). The recurrence rate was 51.72%, but symptoms of 27 recurrence cases were lighter than pre-treatment. All treatments were well tolerated, and no serious adverse events occurred. CONCLUSION: The reasonable combined modality therapy is aimed at the complicated pathogenesis of PAR, and the curative effect is satisfactory, so it is a good way to treat PAR.

Administration, Intranasal↗