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PubMed1987

Definitive combined modality therapy of carcinoma of the anus. A report of 30 cases including results of salvage therapy in patients with residual disease.

Thirty patients with epidermoid carcinoma of the anus, ranging in age from 40 to 89 years, were treated with combined chemotherapy (CT) and radiation therapy (RT) in lieu of abdominoperineal resection. Two courses of 5-FU (1000 mg/m2/day X four days) by continuous infusion and mitomycin-C (10-15 mg/m2 IV bolus on day 1 of each course) were given 3 to 4 weeks apart simultaneously, with whole pelvis RT to 4140 to 4500 cGy. Twenty-one of 28 patients had T3-T4 primaries and ten had positive nodes (N1). Two of the 30 patients were treated for local recurrence following surgical excision and one was treated immediately after local excision. Twenty-six of the 30 patients attained biopsy-confirmed complete remission. Four of the 30 patients demonstrated residual disease at completion of therapy but all subsequently achieved complete remission with additional nonsurgical treatment. One patient, initially treated for local recurrence following excision failed locally at four years and was salvaged with chemotherapy followed by abdominoperineal resection. No patient has experienced distant failure. Twenty-seven of 30 patients were alive and disease free after 9 to 76 months of follow-up and three died, disease-free, of unrelated causes. Acute toxicities were mild and did not necessitate interruption of treatment. A brisk perineal reaction and diarrhea were noted in all patients. Late complications were unusual. All patients were treated in a community-based, private practice setting. The authors conclude that combined CT-RT, as employed herein, represents a first-line curative treatment for the majority of patients with epidermoid anal carcinoma. For patients who demonstrate residual disease following this therapy, salvage regimens such as 5-FU infusion and cisplatin, or sequential MTX-5-FU-Leucovorin with additional synchronous RT should be employed before resorting to radical surgery.

Adult↗
PubMed1993

Chemotherapy and combined modality therapy in head and neck cancer.

Chemotherapy for head and neck cancer is being actively investigated. Trials of cisplatin, infusional fluorouracil, and other new agents highlight the need for better therapies for patients with recurrent disease. Induction chemotherapy, concomitant chemoradiotherapy, and rapid-sequence combined therapy have been shown to be feasible treatments with encouraging results. Rapidly alternating chemoradiotherapy has been shown to result in a survival benefit compared with radiotherapy alone. Biologic therapy, including interferon and interleukin-2, also merits future evaluation in clinical trials.

Carcinoma, Squamous Cell↗
PubMed1986

Second neoplasms in patients with Hodgkin's disease following combined modality therapy--the Yale experience.

From 1969 to 1982, 183 patients with previously untreated stages IIIB and IV Hodgkin's disease and relapsing Hodgkin's disease after radiation therapy were treated with combination chemotherapy plus low-dose irradiation (CRT). One hundred fifty patients who achieved a complete response (CR) were analyzed for risk of developing a second neoplasm. Median follow-up has been 8.3 years. Actuarial survival of all patients is 74% at 10 years with a relapse-free survival of 68%. An additional 24 patients with stage IIIA disease were also treated with CRT. There were 22 CRs at risk who were analyzed. Median follow-up has been 3+ years with an actuarial survival of 90% at five years and a relapse-free survival of 83%. Second neoplasms have developed in 14 of 172 patients at risk: acute nonlymphocytic leukemia (ANLL; five patients); aggressive histology non-Hodgkin's lymphoma (NHL; three patients); and a variety of solid neoplasms (six patients). Time to second neoplasm diagnosis after initial treatment ranged from 12 to 141 months. Five patients were older than 40 years. At the time of diagnosis of the second malignancy, 11 patients were free of Hodgkin's disease (for 36 to 141 months) and three were receiving therapy for recurrent Hodgkin's disease. The 10-year actuarial risk (%) of developing ANLL was 5.9 +/- 2.8; for NHL, the risk was 3.5 +/- 2.4, and for solid neoplasms, 5.8 +/- 3.0. Our results suggest that combination chemotherapy plus low-dose irradiation does not appear to significantly increase the risk of developing second neoplasms above that already reported for combination chemotherapy when administered as either initial or salvage treatment of Hodgkin's disease.

Actuarial Analysis↗
PubMed2004

Early-stage non-small-cell lung cancer: current perspectives in combined-modality therapy.

The most effective treatment for patients with early-stage non-small-cell lung cancer (NSCLC) remains complete surgical resection, providing the disease is medically operable and adequately staged. The effectiveness of surgical resection, however, is limited by high rates of distant recurrence caused by the presence of metastatic disease that is not apparent at the time of surgery. Thus, induction, adjuvant chemotherapy, and radiation therapy, as well as a combination of both, have been studied for their ability to reduce local and distant recurrence rates and to improve survival. Adjuvant chest radiation therapy following resection decreases local relapse rates but also decreases overall patient survival, with an increase in the hazard ratio of death. A previous metaanalysis of cisplatin-based adjuvant chemotherapy showed a 13% reduction in the hazard ratio of death and a 5% improvement in 5-year survival, but the differences in the small sample failed to reach statistical significance. Newer 2-drug combinations were shown to reduce the hazard ratio of death by 14%, with a 4.3% improvement in 5-year survival in the largest trial recently reported. These newer 2-drug combinations also have the benefits of reduced toxicity and improved delivery. Induction chemotherapy offers several potential advantages compared with adjuvant chemotherapy, such as improved delivery, early control of micrometastatic disease, and reduction of the primary tumor size prior to surgery, thus allowing for more conservative and possibly complete resection of the tumor. A number of clinical trials have shown that induction chemotherapy is safe and feasible, with no significant increase in surgical complications, and results in favorable survival rates in patients with resectable NSCLC. A number of phase III randomized trials are currently under way to confirm the benefits of induction chemotherapy in patients with stage IB-IIIA NSCLC and to compare induction chemotherapy versus adjuvant chemotherapy following surgery versus surgery alone. In addition, biologically targeted agents are currently under study for patients with advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Cervical cancer--phase III studies of radiation therapy combined modality].

The number of patients with cervical cancer has been constantly reduced but it remains a leading cause of death among gynecologic malignancies in Japan. In 1990, 5,793 patients with cervical cancer were registered and 1,892 cases (32.7%) were stage 0, 2,074 cases (35.8%) were stage I, 991 cases (17.1%) were stage II, 659 cases (11.4%) were stage III and 172 cases (3.0%) were stage IV. Among these patients, about 40% were treated with radiation therapy alone or combined with radiation therapy. The five-year survival rates of stage I, II, III, and IV patients were 83.4%, 65.3%, 40.3% and 13.1%, respectively. Phase III studies have been conducted to compare surgical treatment and radiation therapy, and it is clarified that radiation therapy is equivalent to surgical therapy in young healthy patients with an early-stage tumor, while combined radiation therapy followed by surgery did not improve results over radiation alone. It is thus justified to offer postoperative irradiation to selected patients who have high-risk factors in the surgical specimen. Effects of chemotherapy were also compared to radiation therapy. Multiagent chemotherapy such as bleomycin, vincristine, mitomycin C, and cisplatin or bleomycin, ifosphamide and cisplatin are standard regimens for cervical cancer. However, because the toxicity of chemotherapy along with radiation therapy is much higher than that of radiation alone, there is a need to develop an adequate adjuvant chemotherapy regimen for cervical cancer. Other ongoing trials are also discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Is combined modality therapy appropriate for apparently localized carcinoma of the prostate?

In a pilot study at the authors' institution, 17 patients with stage C carcinoma of the prostate had preoperative therapy with diethylstilbestrol. After 8 to 12 weeks of DES at 3 mg per day, the surgical margins, seminal vesicles, and pelvic lymph nodes were free of tumor in seven patients. In one patient, no residual tumor could be found despite an extensive search, and in two other cases, only small foci of atypical cells could be found. The authors suggest a trial of the proper role of neoadjuvant hormonal therapy in stages B2 and C prostatic carcinoma.

Animals↗
PubMed1982

Combined modality therapy for advanced Hodgkin's disease: long-term followup data.

From 1969 to 1979, 155 patients with advanced Hodgkin's disease were treated with a combined modality protocol (combination chemotherapy and irradiation to all sites of disease). The actuarial 10-year survival of all patients who started therapy is 78%, and the relapse-free survival is 67%. Within the group of patients with advanced disease, age greater than 40 years and/or stage IV disease with multiple extranodal sites of involvement adversely affected prognosis. Since 1978, these patients have been treated with MOPP-ABVD and irradiation, with a resulting 3-year survival of 87% compared with 58% for those treated with MVVPP in prior years. A comparison between MVVPP and MOPP, also begun in 1978, has thus far yielded no significant differences. Second malignancies have occurred in four patients apparently cured of their Hodgkin's disease: two patients with acute leukemia and two with non-Hodgkin's lymphoma. Avascular necrosis of bone has developed in nine patients. There have not been other serious long-term complications. This combined modality treatment approach appear to offer a significant survival advantage compared with treatment programs using chemotherapy alone.

Adult↗
PubMed1997

Combined-modality therapy for squamous carcinoma of the buccal mucosa: treatment results and prognostic factors.

BACKGROUND: Reports on locoregional control and survival of squamous cell carcinoma of buccal mucosa are scarce in literature. In this study, a single institutions's experience of combined surgery and postoperative radiotherapy (RT) for buccal mucosal malignancy with favorable results was analyzed and presented. The prognostic factors on locoregional control were also discussed. METHODS: From January 1988 to July 1994, 57 patients with squamous cell carcinoma of buccal mucosa treated by surgery and RT were reviewed. The distributions according to American Joint Committee on Cancer (AJCC) staging were: stage II, 6; stage III, 21; and stage IV, 30 patients. Total dose of RT at the buccal area ranged from 45 Gy to 68.4 Gy, median 61.2 Gy. Tumor-related factors (AJCC stage, T stage, histologic grading, pathologic tumor invasion to skin of cheek, adjacent bony structures, and regional lymph nodes) and treatment-related factors (surgical margin, radiation dose, and the time interval between operation and RT) were analyzed to determine their influence on locoregional control. RESULTS: Three-year actuarial locoregional control rate, overall survival rate, and disease-specific survival rates were 64%, 55%, and 62%, respectively. Ten of these 22 patients (45%) with recurrent tumors were reoperated, but only 2 patients were successfully salvaged. Positive surgical margin and tumor invasion to skin of cheek were significantly poor prognostic factors on locoregional control by univariate analysis. In multivariate analysis, tumor invasion to skin of cheek was the only prognostic factor (p = .0014). CONCLUSIONS: Locoregional failure was the major cause of death for squamous buccal mucosa cancers managed with surgery and RT. Few recurrences could be detected early and successfully salvaged. Skin of cheek involvement is an important prognostic factor for buccal mucosa cancers.

Actuarial Analysis↗
PubMed2002

Combined modality therapy following bladder conservation surgery for bladder cancers.

OBJECTIVE: To analyze the efficacy of recurrence prophylaxis using radiation and chemotherapy following bladder conservation surgery for muscle invasive bladder cancer. METHODS: 23 patients with muscle invasive bladder cancer were treated with radiotherapy combined with bladder mitomycin infusion after bladder conservation surgery (study group). Radiotherapy was given using an external beam at an average dose of 5148 +/- 462 cGy with conventional fractionation. For comparison, 29 similar patients treated with postoperative bladder mitomycin infusion without radiation served as control (control group). All patients were followed up for more than 3 years, an average of 41.6 months (36 - 60 months). RESULTS: The 3-year pelvic recurrent rate of muscle invasive bladder cancer was 17.4% in the study group and 44.8% (P = 0.036) in the control group. The 3-year distant metastasis rates were 17.4% and 24.1%, respectively (P = 0.554). The 3-year overall survival rates were 81.8% and 86.2%, respectively (P = 0.670). Two patients from the study group had their treatment interrupted, one for 3 days and the other for one week due to acute cystitis, while the rest of the patients were able to complete the treatment according to schedule. CONCLUSION: Radiotherapy plus chemotherapy after bladder conservation surgery for muscle invasive bladder cancer can decrease the rate of pelvic recurrence effectively and be used as a realistic adjuvant treatment.

Adult↗
PubMed1999

Combined-modality therapy for locoregionally advanced head and neck cancer.

Traditionally, treatment for locally advanced resectable head and neck cancer has been surgical resection followed by postoperative radiation. In unresectable patients, primary radiation has been the mainstay of treatment. In an attempt to improve local control and survival, chemotherapy has been investigated as an adjunct to locoregional treatment. Induction or adjuvant chemotherapy in combination with primary surgical resection has failed to demonstrate an improvement in either local control or survival. Induction chemotherapy followed by radiation therapy is an acceptable alternative to surgical resection for organ preservation. A randomized trial in patients with advanced oropharyngeal carcinoma and another in advanced nasopharyngeal carcinoma have shown an improvement in survival with the use of concomitant chemotherapy and radiation compared to radiation alone. Other prospective randomized trials as well as three meta-analyses also demonstrate improved survival with the addition of concomitant chemotherapy for locally advanced disease. Newer chemotherapeutic agents are currently under investigation, particularly those with radiosensitizing properties. Chemotherapy as part of primary therapy, however, should be used judiciously, and should be based on an assessment of the potential risks and benefits to each patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

High rate of prolonged remissions following combined modality therapy for patients with localized low-grade lymphoma.

PURPOSE: Involved field (IF) radiation can cure as many as 40% to 50% of patients with stage I-II low-grade lymphoma. We sought to improve these results by prospectively evaluating the combination of IF radiation and chemotherapy consisting of 10 courses of cyclophosphamide, vincristine, prednisone, and bleomycin, with doxorubicin added in a risk-adapted manner (COP/CHOP-Bleo). PATIENTS AND METHODS: From 1984 until December 1992, 91 patients, median age 56 years (range 28 to 77 years), with clinical stage I-II low-grade lymphoma were treated. No patients were excluded on the basis of age or organ function. RESULTS: A complete response was attained in 99% of evaluable patients. Treatment-related toxicity was mild, and no deaths occurred during therapy. With a median follow-up of 60 months, there have been only 16 relapses. The actuarial freedom from relapse rate at five years is 82% (95% confidence interval 71% to 89%) and at 10 years is 73%. At five years the overall survival rate is 90% (95% confidence interval 81% to 95%) and at ten years it is 82%. Of the clinical features examined, only older age (> 56 years; p = 0.07) was associated with shorter survival. No features examined were predictive of disease relapse. CONCLUSION: The combination of IF radiation and risk-adapted COP/CHOP-Bleo chemotherapy is well-tolerated, produces a very high rate of complete remission, and with a median follow-up of five years, has produced lower rates of relapse and better overall survival than has been reported for IF radiation alone in patients with clinically-staged I-II low-grade lymphoma.

Adult↗
PubMed2006

Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials.

PURPOSE: In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control. PATIENTS AND METHODS: Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT. RESULTS: Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175). CONCLUSION: A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.

Adolescent↗
PubMed1977

Chemoimmunotherapy of a murine fibrosarcoma: critical factors for success of combined modality therapy.

Thiabendazole (TBZ), a new nonspecific immunopotentiator, was evaluated in combination with Cytoxan in the therapy of a syngeneic murine fibrosarcoma. The reduction of tumor burden by chemotherapy was critical in achieving an optimal response from immunotherapy. Eighty-eight percent of the mice that responded to Cytoxan had sustained regression of tumor with TBZ treatment. The response to TBZ was markedly diminished, both in duration and magnitude, in the mice considered to be Cytoxan nonresponders. Timing of immunotherapy was also important. If Cytoxan and TBZ were given simultaneously, growth kinetics similar to those observed with Cytoxan alone were observed. However, if TBZ was given 4 days after Cytozan administration, prolonged regression of tumor was seen. Alone, TBZ was most effective at a dose of 20 mg/kg. However, in combination with Cytoxan the most effective dose was 0.2 mg/kg. The implications of this finding are discussed.

Animals↗
PubMed1979

ICRF-159 enhancement of radiation response in combined modality therapies. II. Differential responses of tumour and normal tissues.

The combined effect of the chemotherapeutic agent ICRF-159 and radiation on the proliferative status of tumor/normal systems has been evaluated using the Lewis lung tumour in BDF1 mice. We have previously shown that a 25 mg/kg dose of ICRF-159, given at 3h intervals X4 before irradiation, significantly enhanced tumour growth retardation relative to a single dose of 100 mg/kg before irradiation. Whilst both single and fractionated drug treatments produced a transient inhibition of cell proliferation, comparisons of the temporal recovery from the antiproliferative effect of radiation in both tumour and intestinal epithelium suggested that single acute doses of ICRF-159 fail to potentiate the radiation response of either tissue. Protracted drug administration before irradiation, however, markedly decreases the post-radiation proliferative recovery of the tumour, without significantly altering intestinal recovery. The data suggest that both drug concentration and/or exposure time determine the interactions seen with combined modes.

Animals↗
PubMed1992

Combined-modality therapies for non-small cell lung cancer.

Regionally advanced stage III non-small cell lung cancer (NSCLC) accounts for nearly 40% of all presentations of NSCLC. In the past, such patients received radiotherapy alone, but the median and long-term survival durations were disappointingly poor. Past attempts at combining chemotherapy and radiation were also disappointing, and were troubled by low doses of radiation or orthovoltage equipment or both. Recently, cisplatin-containing regimens have shown some efficacy in stage IV disease. The response rate for these combinations in stage III disease is nearly double that in stage IV disease. The greater response in stage III has led to a series of trials of sequenced chemotherapy and radiotherapy for treatment of regionally advanced (unresectable stage IIIA and IIIB) NSCLC. Several randomized trials have now shown a statistically significant advantage for the combined modality over radiation alone regarding time to treatment failure, median survival duration, and percent of long-term survivors. Other trials have focused on the concurrent use of chemotherapy and radiotherapy. Several pilot studies have suggested that concurrent cisplatin plus chest irradiation can produce apparently beneficial results with respect to local control and are the subject of ongoing clinical trials. At the University of Maryland Cancer Center, we have combined weekly carboplatin 100 mg/m2 with concurrent chest irradiation. The preliminary results are very encouraging. The toxicity of this treatment program is very manageable, and preliminary data suggest excellent local control and survival. Other pilot studies have suggested that combination chemotherapy with concurrent radiotherapy is also technically feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Combined modality therapy of A431 human epidermoid cancer using anti-EGFr antibody C225 and radiation.

BACKGROUND: Monoclonal antibodies (mAb) to epidermal growth factor receptor (EGFr) inhibit tumor cell proliferation and enhance cytotoxicity of chemotherapeutic agents. The purpose of this study was to investigate the interaction of the anti-EGFr antibody C225 combined with radiotherapy (RT) on EGFr expressing A431 human epidermoid cancer cells. METHODS: Cell proliferation, apoptosis, EGFr expression and phosphorylation, and clonogenic survival were assayed in vitro. A431 tumor growth inhibition and immunohistochemistry analysis of EGFr expression and apoptosis were assessed in vivo. RESULTS: C225 plus RT produced greater inhibition of A431 cell proliferation than C225 or RT alone which was corroborated by enhanced apoptosis. Similar clonogenic survival occurred following the addition of C225 to RT, although colonies were smaller in the presence of C225. C225 produced inhibition of EGF-induced phosphorylation of EGFr without concurrent down-regulation of surface receptor, which was not altered by RT. Combined treatment of mice bearing tumors demonstrated enhancement of complete regressions, reduction in time to tumor size doubling, and prolongation of survival. Significant apoptosis occurred in xenograft tumors treated with C225 with or without RT. CONCLUSIONS: These data demonstrate an interaction between C225 and RT. C225-mediated apoptosis and inhibition of EGFr phosphorylation may be critical in the interaction. Studies to define the precise influence of combined modality treatment on the EGFr signal transduction cascade need to be pursued. The combination of growth factor receptor antibodies and RT has potential application in clinical oncology.

Animals↗
PubMed2005

Combined modality therapy for limited-disease small cell lung cancer.

Small Cell Lung Cancer (SCLC) is highly sensitive to chemotherapy and radiotherapy. However, despite initial responses, relapses are common and most patients eventually succumb to this disease. Patients with limited-disease SCLC represent approximately 30% of all patients with SCLC, and are potentially curable when treated with combined chemotherapy and thoracic radiotherapy (TRT). Chemotherapy consists of four cycles of the combination of cisplatin and etoposide (PE). Thoracic radiotherapy should be started with the first or second cycle of chemotherapy, and preferably administered twice daily for 3 weeks. Prophylactic cranial irradiation (PCI) is recommended for patients who achieve a complete response. Surgery is of limited value in SCLC, except in patients who present with a solitary pulmonary nodule. Approximately 20% to 25% of patients with limited disease (LD)-SCLC can be cured with this aggressive approach. Newer treatment modalities are currently under investigation.

Antineoplastic Combined Chemotherapy Protocols↗