Polymer-conjugated paclitaxel as a radiosensitizing agent--a big step forward for combined modality therapy?
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Antineoplastic Agents↗
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Results for “Combined Modality Therapy”
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Models of normal tissue injury following combined modality therapy.
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Antineoplastic Agents↗
[Surgery and combined modality therapy of esophageal cancer].
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Combined Modality Therapy↗
Diagnostic imaging and combined modality therapy of rectal cancer.
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Combined Modality Therapy↗
Combined modality therapy for advanced Hodgkin's disease: 15-year follow-up data.
From 1969 through 1982, 184 patients with advanced Hodgkin's disease (HD) were treated with combined modality therapy (CMT) at Yale University. The data were reanalyzed in November 1986, with a mean follow-up of 10 years. The patient population consisted of 102 newly diagnosed stages IIIB and IV patients, and 82 patients who had relapsed after initial radical radiotherapy. From 1969 through 1978, the treatment program was induction chemotherapy with nitrogen mustard, vincristine, vinblastine, procarbazine, and prednisone (MVVPP) for three cycles (6 months) followed by low-dose radiation (1,500 to 2,500 cGy) for patients who had achieved complete remission (CR), to all disease sites present before the onset of chemotherapy. From 1978 to 1982, selected "poor-risk" advanced-stage patients received nitrogen mustard, vincristine, procarbazine, prednisone plus Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (MOPP-ABVD) induction chemotherapy, while the remaining patients were randomized between MVVPP and MOPP. One hundred fifty-one patients have achieved CR (82%); 23 (15%) of these 151 have relapsed, with the remaining 128 patients in continuous CR. A total of 62 patients have died, 45 due to HD, and 17 due to other causes. Twelve of these 17 patients died of second malignancies. The 15-year actuarial survival of all patients is 54%. It is 71% if deaths due only to HD are considered. Within the overall group of advanced HD patients, age and multiple extranodal sites of involvement continue to constitute adverse risk factors. The three drug programs used were all equivalent. No improvement resulted from the use of MOPP-ABVD in the poor-risk patients. These results compare favorably with those recently published by the National Cancer Institute (NCI). CMT resulted in an approximate 20% improvement in survival with no increase in second malignancies when compared with chemotherapy alone.
Adult↗
Irinotecan in combined-modality therapy for locally advanced non-small-cell lung cancer.
The management of non-small-cell lung cancer is undergoing rapid evolution. Although the advent of combined-modality therapy has led to improved survival, most patients eventually succumb to the disease. The arrival of a new generation of chemotherapeutic agents--including the taxanes, gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar, CPT-11)--offers the hope of advances against this malignancy. Irinotecan, a camptothecin derivative, has shown impressive activity in a variety of solid tumors, including non-small-cell lung cancer. It is believed to act by stabilizing the topoisomerase-DNA complex formed during diverse cellular processes, including replication and transcription. A considerable body of evidence also demonstrates that camptothecin and its derivatives possess substantial radiosensitization properties. This article will review the in vitro and in vivo data on irinotecan's ability to render tumors more susceptible to ionizing radiation. It will then focus on experience with irinotecan and thoracic radiation in the treatment of non-small-cell lung cancer, which has yielded acceptable toxicity results and response rates in excess of 60% in early trials. It is hoped that newer treatment strategies--such as the combination of radiation and irinotecan in lung cancer--will significantly impact cure rates in the future.
Antineoplastic Agents, Phytogenic↗
Combined modality therapy of extrahepatic biliary system cancer.
From January 1985 to December 1988, 10 patients with local/regional extrahepatic biliary system cancer (gallbladder: 2, Klatskin: 4, common bile duct: 4) underwent combined modality therapy. Laparotomy and biopsy or subtotal resection were performed in six patients and endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiogram, and biliary drainage in four patients. Patients initially received 5000 cGy to the tumor bed and primary nodal area. Eight received an additional 1500 cGy boost to the tumor bed. Chemotherapy (5-FU/mitomycin-C) was delivered at the beginning of each radiation treatment course. Four patients received an additional 1-4 cycles of maintenance chemotherapy and six received a boost with brachytherapy. The mean survival was 32 months and the median survival was 16 months. Five patients are currently NED at 16, 17, 17, 48, and 52 months. The overall 3-year actuarial survival was 50%. The cumulative incidence of failure as a component of failure was local/regional: 50%, abdominal: 40%, and distant: 10%. Of the five patients who developed failure, all developed a component of local/regional failure. Our data show that this approach is feasible and offers similar results to those reported in the literature. However, further follow-up will be needed to determine if this combined modality approach offers improved local control and survival rates compared with surgery or biliary bypass/drainage alone.
Biliary Tract Neoplasms↗
High-dose chemotherapy with autologous hematopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer.
PURPOSE: To evaluate the feasibility of high-dose chemotherapy (HDC) with autologous hematopoietic progenitor-cell support (AHPCS) as part of combined modality therapy (CMT) in patients with inflammatory breast cancer (IBC). PATIENTS AND METHODS: From April 1993 to March 1997, 30 patients with IBC were treated at our program. Twenty-three patients received neoadjuvant chemotherapy (NAC) before HDC; 18 patients also received adjuvant chemotherapy following surgery, but before HDC. All patients received HDC with high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with AHPCS. Every patient underwent surgery either before (27 patients) or after (three patients) HDC. Patients received radiotherapy after HDC in addition to tamoxifen if their tumors were estrogen receptor-positive. RESULTS: Thirteen patients experienced grade 3 or 4 nonhematologic noninfectious toxicities. In 12 patients (40%), this represented drug-induced lung injury, which in all cases responded to a 10-week course of corticosteroids. The only treatment-related death was secondary to hemolytic-uremic syndrome (HUS). Another patient suffered grade 4 CNS toxicity, which was completely reversible. All patients engrafted promptly. Eight patients relapsed, five of whom had a poor pathologic response to NAC. Relapses were local (five patients), local plus systemic (one), or systemic only (two). Median follow-up time from diagnosis and HDC is 23.5 (range, 7 to 49) and 19 (range, 4 to 44) months, respectively. Twenty-one patients (70%; 95% confidence interval [CI], 51% to 86%) remain alive and free of disease 4 to 44 months after HDC. Median disease-free survival (DFS) and overall survival have not yet been reached. CONCLUSION: HDC as part of CMT is feasible in patients with IBC. The toxicity of this treatment program is significant, but tolerable. Despite the short follow-up duration, the promising DFS observed in this group of patients warrants randomized studies that include a HDC-containing arm in patients with IBC.
Adenocarcinoma↗
Combined modality therapy of Hodgkin's disease: 10-year results of National Cancer Institute of Canada Clinical Trials Group multicenter clinical trial.
The purpose of this study was to compare four methods of treatment for stage III-IV Hodgkin's disease. Between January 1972 and September 1976, 266 patients with stage IIIB, IVA, and IVB Hodgkin's disease from 21 cancer treatment centers across Canada were registered as eligible; 40 were found to be ineligible. Of the 226 remaining patients, only seven were followed for less than 10 years. All patients received three courses of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, which induced a complete response (CR) in 36%; an additional 42% obtained adequate disease control. Patients were randomly assigned to (1) treatment with radiation to the abdomen and mantle (group AX3, 62 patients) or (2) continue their treatment with an additional three courses of MOPP (group A, 105 patients). For the A group, a second randomization took place 3 months later (regardless of status at that time) to (1) no further treatment (AC6, 23 patients), (2) radiotherapy to the abdomen and mantle (AX6, 48 patients), or (3) maintenance chemotherapy at 3-month intervals for 1 year (AC10, 26 patients). The survival of AX3 patients was somewhat better than for the A group, but the difference was not significant (P = .0565). However, there was a significant interaction (P = .0029) between age and treatment, so that among patients less than 30 years of age, the survival of the A group was better, whereas for older patients, treatment with AX3 resulted in improved survival. Age itself remained a significant prognostic factor for survival after controlling for the amount of radiotherapy delivered to the abdomen and the dose intensity of vincristine for the first three courses of chemotherapy. The addition of radiation therapy to MOPP significantly reduced the frequency of nodal relapses. These results suggest that combined modality therapy may be beneficial for some patients with Hodgkin's disease and that age must be carefully considered in interpreting the results of clinical trials in Hodgkin's disease.
Adolescent↗
Age is independent of comorbidity influencing patient selection for combined modality therapy for treatment of stage III nonsmall cell lung cancer (NSCLC).
OBJECTIVES: To determine the influence of age and comorbidity in patient selection for treatment of stage III NSCLC with combined modality therapy (CMT). METHODS: There were 102 patients with a Karnofsky Performance Score greater than or equal to 70, and clinical stage III NSCLC analyzed retrospectively for comorbidity. All patients received radiotherapy, and 57 (56%) received CMT with sequential and/or concurrent chemotherapy. Comorbidity was rated retrospectively using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). The effect of an extremely severe comorbidity score on patient selection and overall survival (OS) was evaluated. RESULTS: Presence of a grade 4 comorbidity (P = 0.02) and use of radiation only (P < 0.01) were associated with a statistically significant inferior OS on multivariate analysis, whereas age greater than or equal to 70, clinical stage IIIB, >5% weight loss, and radiation dose >63 Gy were not. Patients receiving CMT were significantly younger (P < 0.001), with less comorbidity (P < 0.001), and weight loss (P = 0.003) compared with patients receiving radiotherapy alone. A multivariate analysis revealed that age (P < 0.001), comorbidity (P = 0.007), and weight loss (P = 0.002) were independent factors influencing patient selection for CMT. CONCLUSIONS: Age effects patient selection for CMT independent of comorbidity and weight loss in patients with stage III NSCLC and good performance status. This might be related to physician's biases regarding tolerability of CMT in the elderly, and might explain under-representation of elderly in clinical trials of lung cancer. Comorbidity assessment should be included in protocols studying locally advanced stage NSCLC and may be useful for stratification.
Age Factors↗
Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer.
OBJECTIVE: Our aims were to (1) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy (CMT) followed by total mesorectal excision (TME), (2) identify factors predictive of oncologic outcome, and (3) determine the oncologic significance of the extent of pathologic tumor response. SUMMARY BACKGROUND DATA: Locally advanced (T3-4 and/or N1) rectal adenocarcinoma is commonly treated with preoperative CMT and TME. However, the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown. METHODS: Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6 cm from the anal verge (range 0-15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5-fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A prospectively collected database was queried for long-term oncologic outcome and predictive clinicopathologic factors. RESULTS: With a median follow-up of 44 months, the estimated 10-year overall survival (OS) was 58% and 10 year recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic response >95%, lymphovascular invasion and/or perineural invasion (PNI), and positive lymph nodes were significantly associated with OS and RFS. Patients with a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P = 0.002). CONCLUSIONS: Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study.
Adenocarcinoma↗
[Effective combined modality therapy for a patient with primary adrenal lymphoma].
Primary adrenal lymphoma is a rare lymphoma with clinical features consisting of a high incidence of bilateral adrenal involvement, diffuse large B-cell histology and secondary adrenal insufficiency. We report a successful treatment of a patient with primary adrenal lymphoma using a combined modality therapy (CMT). A 62-year-old man was hospitalized with pain of the flank, and a computed tomography (CT) scan of the abdomen revealed very large, bilateral adrenal masses. A needle biopsy of the left adrenal mass revealed diffuse large B-cell lymphoma. After irradiation of both adrenal lymphomas and CHOP therapy accompanied by intrathecal treatment and rituximab, the patient underwent a left adrenalectomy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation. The patient has been disease-free for 2 years after the diagnosis of primary adrenal lymphoma. In contrast to the previous reports of poor response to conventional-dose chemotherapy alone and short-term survival of patients with primary adrenal lymphoma, our patient has demonstrated that radiation therapy combined with chemotherapy and rituximab may be an effective modality as a first-line therapeutic regimen for localized primary adrenal lymphoma.
Adrenal Gland Neoplasms↗
Past, current and future protocols for combined modality therapy in childhood medulloblastoma.
Radiotherapy plays a major role in the management of brain tumors, together with surgical resection and more recently, chemotherapy. Improved efficacy of radiotherapy, ranging from novel techniques of radiotherapy to combination with (new) chemotherapeutic drugs or agents that selectively target tumor cells, are currently being explored and offer some hope for improvement of the prognosis of primary brain tumors. This approach might also enable reducing radiation doses, thereby potentially decreasing the risk of severe late effects in pediatric brain tumor patients. This review will evaluate past, current and future treatment approaches of combined modality therapy in childhood medulloblastoma.
Antineoplastic Agents↗
Combined modality therapy for HIV-infected patients with squamous cell carcinoma of the anus: outcomes and toxicities.
PURPOSE: We report toxicity and survival data of human immunodeficiency virus (HIV)-infected men with anal carcinoma treated with combined modality therapy (CMT) of radiotherapy and concurrent chemotherapy. METHODS AND MATERIALS: A retrospective review was performed on the records of 17 HIV-positive patients with anal squamous cell carcinoma treated with CMT at our institution between 1991 and 2004. Radiotherapy consisted of 30.6 to 45 Gy to the pelvis, total dose of 50.4 to 59.4 Gy to initial gross disease, at 1.8 Gy/fraction. Chemotherapy consisted of 5-fluorouracil and either mitomycin C or cisplatin. The mean follow-up was 25.6 months (median, 15.6 months; range, 4.6-106 months). RESULTS: Significant acute skin and hematologic toxicity developed in 8 of 17 and 9 of 17 patients, respectively. One patient died 12 days after treatment of progressive disease and sepsis. Significant late toxic sequelae developed in 3 patients: 1 anorectal ulcer, 2 dermatologic (perianal ulceration, hemorrhagic perineal sores and suspected fissure). Fourteen of 15 patients with Stage I-III disease had a complete response; 2 complete responders subsequently had a relapse in the anorectum. For all patients, actuarial 18-month survival was 67%. For patients with Stage I-III disease, survival at last follow-up by low CD4 count (<200) vs. high count (>200) was 4 of 7 vs. 7 of 8, respectively; significant acute toxicities developed in 4 of 8 vs. 6 of 9, respectively. CONCLUSION: For HIV patients with anal carcinoma, CMT yields reasonable local control with significant acute complications. Survival is lower than in the general population, attributable more to the underlying infection than to the malignancy.
Adult↗
Front-line high-dose therapy with autologous stem cell transplantation for high risk Hodgkin's disease: comparison with combined-modality therapy.
This retrospective study compares high-dose therapy (HDT) with autologous stem cell transplantation and combined-modality treatment (CT) as a first-line therapy for Hodgkin's disease (HD) for patients with both a clinical stage (CS) IV and/or a mediastinal mass > or =0.45 of the thoracic diameter (MM > or =0.45) at diagnosis, and an incomplete response after the first-line chemotherapy. Data on 42 grafted patients (GP) in Nantes Hospital, France and on 108 combined-modality treated patients (CTP) from two protocols of the GOELAMS group, France (POF 81 and H90) was analyzed. Both groups were comparable except for pulmonary disease in excess in the grafted group (P = 0.01). Among GP, 95% were in complete response at the end of first-line treatment and 77% among CTP. Median follow-up was 53 months (range, 7 to 128 months) for GP and 88 months (range, 25 to 181 months) for CTP. The 5-year freedom from progression (FFP) and event-free survival (EFS) rates were better for GP (87% vs 55% for FFP: P = 0.0004 and 81% vs 51% for EFS: P = 0.0004) whereas the overall survival (OS) rates did not differ significantly (85% for GP vs 71% for CTP: P = 0.06). Similar results were obtained for the groups with a response > or =50% after initial chemotherapy: 91% vs 65% for FFP, P = 0.01; 87% vs 61% for EFS, P = 0.02; and 92% vs 77% for OS, P = 0.2; and for the groups with a response <50%: 80% vs 22% for FFP, P = 0.0003; 72% vs 13% for EFS, P = 0.0001; and 76% vs 46% for OS, P = 0.04. This study shows a better control of the disease with HDT.
Adolescent↗
Combined-modality therapy in pancreatic cancer: current status and future directions.
The use of chemotherapy with concurrent radiation therapy remains a standard treatment option for patients with unresectable or resected adenocarcinoma of the pancreas. This treatment strategy is based in large part on data from serial Gastrointestinal Tumor Study Group (GITSG) trials, which have included 5-fluorouracil (5-FU). Unfortunately, the majority of patients continue to succumb to the disease process. Recently, there has been a resurgence in clinical trials investigating alternative combined modality treatment strategies for patients with pancreatic cancer. In this review, we will summarize both the mature and more recent data pertaining to combined modality therapy for patients with unresectable or resected pancreatic cancer. Strategies utilizing concurrent gemcitabine, alternative radiation therapy techniques, and/or altered sequencing of therapies will be highlighted. Such modifications to the approach in use since the 1980s will need to be fully considered as clinical trials utilizing chemoradiotherapy regimens and new systemic agents or novel targeted therapies are designed.
Antimetabolites, Antineoplastic↗
Modification of radiosensitivity following chemotherapy exposure: potential implications for combined-modality therapy.
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Antineoplastic Combined Chemotherapy Protocols↗
[Current status of combined modality therapy for esophageal cancer: from the standpoint of medical oncology].
Surgery is considered to be a standard therapy for stage III or the earlier stage of esophageal cancer. However, the standard therapy is changing because of the recent advances in the non-surgical approach, especially chemoradiotherapy. Various obstacles remain to estimate the outcomes of combined modality therapy, while the consensus of the treatment for such stage excluding T4 diseases are as follows: 1) Concurrent chemoradiotherapy has a superior outcome to radiation alone in patients with squamous cell carcinoma. 2) Recent chemoradiotherapy without surgery achieves results comparable to surgery alone. 3) Preoperative chemoradiotherapy can achieve better results than surgery alone in patients with adenocarcinoma. 4) Preoperative chemotherapy is still experimental. Our preliminary results of chemoradiotherapy for esophageal cancer also showed comparable data to extended surgery in terms of survival. Some significant points to be elucidated regarding combined modalities in stage III or earlier are: 1) the comparison of definitive chemoradiotherapy with Japanese extended surgery, and 2) evaluation of efficacy of surgery after chemoradiotherapy. However, these studies require randomized trials comparing surgery with non-surgical treatment, which appears to present significant obstacles. Critical estimation for each study should be recommended based on accurate clinical staging, biological behavior, and intention-to-treat.
Antineoplastic Combined Chemotherapy Protocols↗