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PubMed1986

Combined modality therapy utilizing a cisplatin combination for effective chemotherapy in patients with previously untreated head and neck cancer.

In patients with locally advanced head and neck cancer, the results of standard definitive treatments of surgery, radiotherapy, or both were disappointing. The local and regional recurrence rates were high, despite adequate surgical resection with negative margins and postoperative radiotherapy to all known or possible disease areas. Combination cisplatin chemotherapy given initially before definitive treatments produced a high overall antitumor response and up to 50 percent clinical complete response. Before answering the question of value of chemotherapy as part of the multimodality treatment, it is important to identify the safest and most form of chemotherapy. The degre of chemotherapy effectiveness is defined by the incidence of clinical and, most important, histologic complete response. To assess this effectiveness, chemotherapy was given before definitive treatments to patients with measurable disease. From our 10 year experience we have concluded that continuing the development of induction chemotherapy, including investigating the timing of such effective treatment and assessing the value of such therapy, is of the utmost importance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

The role of UFT in combined-modality therapy.

Fluorinated pyrimidines have long been used as radiosensitizers in combined-modality therapy for solid tumors. Nonetheless, the most commonly used drug, 5-fluorouracil (5-FU), is inconvenient to administer, particularly when given by continuous intravenous infusion. Continuous infusion 5-FU does offer a survival advantage over bolus in the treatment of large bowel tumors. This holds true regardless of whether radiation therapy is concomitantly given. UFT, a combination of uracil and tegafur (in a molar ratio of 4:1), is an attractive alternative. Trials to date suggest at least chemotherapeutic equivalence compared to 5-fluorouracil, and UFT is much simpler to administer. UFT is administered orally and can safely be combined with oral leucovorin. There is profound scientific rationale for using UFT with radiation therapy, and early trials in gastrointestinal malignancies demonstrate the safety and efficacy of the combination. Further studies will determine the optimal timing and uses for concomitant UFT and radiation therapy.

Administration, Oral↗
PubMedDate not supplied

Combined modality therapy for non-small cell lung carcinoma.

Combined modality therapy is frequently used to treat non-small cell lung carcinoma (NSCLC). Surgical resection is the mainstay of treatment for Stages I and II NSCLC. Little evidence supports the use of adjuvant therapy In patients with Stage I NSCLC. Adjuvant radiotherapy to the chest after resection for Stage II and IIIA NSCLC remains controversial but may be appropriate for many patients with resected Stage IIIA disease or inadequately pathologically staged II disease. For Stage IIIA NSCLC, surgery appears suboptimal, though no other single modality appears superior. Recent studies of neoadjuvant therapy for Stage IIIA NSCLC yielded promising results. The standard of care for Stage III unresectable NSCLC and strategies to improve local-regional control in Stage III NSCLC are discussed, as are the importance of toxicity protection with chemoradiation and the potential utility of prophylactic cranial irradiation for preventing brain relapse. Targeted therapies appear promising, and expedited evaluation in Stage III NSCLC is warranted.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Primary combined-modality therapy for esophageal cancer.

Based on positive results from the Radiation Therapy Oncology Group (RTOG) 85-01 trial, the conventional nonsurgical treatment of esophageal carcinoma is combined-modality therapy. Dose intensification of the RTOG 85-01 regimen, examined in the Intergroup (INT)-0123/RTOG 94-05 trial, did not improve local control or survival. Areas of clinical investigation include the development of combined-modality therapy regimens with newer systemic agents, the use of 18F-fluorodeoxyglucose positron-emission tomography to assist in the development of innovative radiation treatment planning techniques, and the identification of prognostic molecular markers. The addition of surgery following primary combined-modality therapy apparently does not improve survival, but this finding is controversial.

Algorithms↗
PubMed1993

Hodgkin's disease with bulky mediastinal involvement: effective management with combined modality therapy.

PURPOSE: To assess results, complications, treatment techniques, and patterns of failure in patients with bulky mediastinal Hodgkin's disease treated with combined modality therapy. METHODS AND MATERIALS: Between 1980 and 1988, 48 patients with Hodgkin's disease who had large mediastinal masses were treated at Stanford University. All patients were staged with clinical studies which included computed tomographic scans of the chest and bipedal lymphograms. Initially, 10 patients underwent staging laparotomy and splenectomy, subsequently all patients were staged by clinical criteria alone. Mediastinal mass ratios ranged from .35 to .85 (mean .46). The majority of patients had at least one site of extralymphatic extension (E-lesion) within the chest. Combined modality therapy included MOPP (prednisone deleted after mediastinal irradiation) in 15, ABVD in 14, and PAVe in 19 patients. All patients received mantle irradiation (mean dose 44 Gy) but only patients with abdominal disease received subdiaphragmatic irradiation. RESULTS: The actuarial survival and freedom from relapse were 84% and 88% at 9 years. There was an intrathoracic component of failure in all seven patients who either failed to achieve an initial complete response or who experienced a relapse after a complete response. Both patients who experienced a relapse after a complete response achieved durable second responses with subsequent chemotherapy. Two of five patients who failed to achieve an initial complete response were treated successfully with alternative chemotherapy. CONCLUSIONS: Routine combined modality therapy is the treatment of choice for patients with Hodgkin's disease who have large mediastinal masses.

Adolescent↗
PubMed1993

[Evaluation of colorectal hepatic metastases with combined modality therapy].

We treated synchronous hepatic metastases in colorectal cancers with combined modality therapy including hepatic resection, selective intra-arterial infusion chemotherapy, and thermocoagulation therapy using a microwave tissue coagulator and compared the value of such therapies. Synchronous hepatic metastases were noted in 563 patients with colorectal cancer who had undergone surgery in our department over the past ten years. Forty-four patients were studied. Six patients underwent hepatic resection only (group A). Another six were subjected to hepatic resection and the residual lesions were treated with selective intra-arterial infusions and thermocoagulation therapy (group B). Fourteen patients were treated with either selective or subselective intra-arterial infusions (group C). The remaining 18 patients were treated in other ways (group D). Cumulative survival, estimated by the Kaplan-Meier method, was compared. One- and three-year cumulative survival rates of patients were 100% and 74% in group A, 100% and 67% in group B, 62% and 0% in group C, and 38% and 5% in group D, respectively. H1 patients accounted for 83% in group A, 33% in group B, 7% in group C, and 22% in group D. The high rate of survival in group A was because of the greater number of H1 patients. One- and three-year survival rated among H2-H3 patients were 100% and 54% in group B, 62% and 0% in group C, and 35% and 14% in group D, respectively. Survival of H2-H3 patients was higher in group B than in group C or D.

Antineoplastic Agents↗
PubMed1988

[AUFRAP therapy: combined modality treatment of malignant gliomas with intraarterial infusion of ACNU].

A method of combination therapy was proposed for the treatment of malignant gliomas, and the clinical results were reported. This combination consisted of ACNU (nimustine), UFT (tegafur + uracil), Radiation, vitamin A and PSK (krestin), and was named AUFRAP therapy. Intracarotid infusion of ACNU (100 or 150 mg/body) was done after the administration of vitamin A (100,000 units), in the first and last week of radiation therapy with a total dose of 60-70 Gy. UFT (400-600 mg/day) and PSK (3g/day) were also given orally. After the induction of remission, patients were treated in the outpatient clinic under a similar maintaining protocol. Two patients who received 150 mg of ACNU and daily 600 mg of UFT in combination with radiation therapy showed severe myelosuppression in the early stage of treatment, and the combination therapy was aborted. Two of four patients who received 100mg of ACNU and daily 400mg of UFT did not show such severe side effects and two showed transient, moderate myelosuppression and vomiting. The serum phenitoin concentration doubled and was thought to be a side effect of tegafur. All four patients completed the induction protocol and follow-up CT scans disclosed shrinkage of the remained tumors, decreased contrast enhancement or no evidence of recurrence. Interactions of these drugs and radiation were discussed and the literature was reviewed.

Adult↗
PubMed2003

Impact of chest wall and lung invasion on outcome of stage I-II Hodgkin's lymphoma after combined modality therapy.

PURPOSE: To examine the impact of extranodal chest wall and lung invasion on the prognosis of patients with clinical Stage I-II Hodgkin's lymphoma treated with combined modality therapy. MATERIALS AND METHODS: The outcome of 324 patients with clinical Stage I-II Hodgkin's lymphoma treated with combined modality therapy between 1981 and 1996 was analyzed. Twenty-two patients had chest wall invasion and 40 had invasion of lung parenchyma. The chemotherapy regimens used were ABVD in 182 patients (56%), MOPP/ABV(D) in 45 (14%), MOPP in 86 (27%), and other chemotherapy regimens in 11 patients (3%). This was followed by mantle/mediastinal radiotherapy (RT) in 163 patients (50%), extended-field RT in 135 patients (42%), and infradiaphragmatic RT in 26 patients (8%). The impact of chest wall and lung invasion on local relapse, disease-free survival, cause-specific survival, and overall survival was examined. RESULTS: After a median follow-up of 8.3 years, the 5-year cause-specific and overall survival rate of the entire cohort was 93% and 90%, respectively. Compared with patients with no extranodal involvement, patients with chest wall invasion had significantly worse local control (89% vs. 68%, p = 0.005), disease-free survival (84% vs. 59%, p = 0.016), and cause-specific survival (94% vs. 86%, p = 0.009). Overall survival was also worse among patients with chest wall invasion, but not significantly so (90% vs. 82%, p = 0.10). Among the 16 patients with chest wall invasion but without lung invasion, 7 progressed during treatment or relapsed, 6 with local failure (crude relapse rate 44%, 95% confidence interval [CI] 19-68%), and 5 died (crude death rate 31%, 95% CI 9-54%). After adjusting for other significant prognostic factors, patients with chest wall invasion had significantly worse local control (hazard ratio 2.8, 95% CI 1.2-6.3), disease-free survival (hazard ratio 2.3, 95% CI 1.1-4.8), and cause-specific survival (hazard ratio 2.8, 95% CI 1.1-6.8). Lung invasion was not significantly associated with any of the outcomes assessed. CONCLUSIONS: Chest wall invasion is an adverse prognostic factor among clinical Stage I-II Hodgkin's lymphoma patients treated with combined modality therapy, although we did not find a worse outcome for patients with lung invasion. Efforts to reduce treatment intensity in these patients should be undertaken with caution, recognizing their increased risk of local relapse.

Adolescent↗
PubMed1984

Combined modality therapy in Stage III and Stage IIIE diffuse large cell lymphomas.

Combined modality therapy consisting of CHOP-Bleo (cyclophosphamide, Adriamycin [doxorubicin], vincristine (Oncovin), prednisone, and bleomycin) and limited-field radiotherapy was given to 47 patients with Stage III and IIIE diffuse large cell lymphomas. Overall 5-year survival and disease-free survival figures are 64% and 53%, respectively. Twenty-nine patients achieved and maintained a complete remission during treatment; 92% of these patients are alive at 5 years, and 87% are disease-free. Prognostic factors were assessed for the entire group. Age, "B" symptoms, extranodal involvement, and extensive abdominal involvement had little effect on survival. However, the presence of mediastinal involvement and extensive abdominal involvement was associated with a poor response rate and survival.

Abdominal Neoplasms↗
PubMed1988

Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group.

Randomized trials of the Gastrointestinal Tumor Study Group have previously demonstrated enhanced survival of patients with locally unresectable pancreatic cancer treated with 5-fluorouracil in combination with radiation therapy compared with that of patients treated with radiation therapy alone. The present study compared the survival of patients treated with multidrug chemotherapy [streptozocin, mitomycin, and 5-fluorouracil (SMF)] versus radiation combined with 5-fluorouracil followed by the same three-drug SMF combination. In 43 patients randomly allocated between these two arms, an improved median survival for the combined-modality therapy (42 weeks) compared with chemotherapy alone (32 weeks) was demonstrated. Overall survival following this combined-modality treatment program (41% at 1 year) was significantly superior to that following SMF chemotherapy alone (19% at 1 year), by a two-tailed log rank test (P less than .02). Serial studies of the Gastrointestinal Tumor Study Group with patients with locally unresectable pancreatic adenocarcinoma have shown that combined-modality therapy is superior to either optimal radiotherapy or chemotherapy alone.

Adenocarcinoma↗
PubMed2000

Combined modality therapy for unresectable stage III non-small cell lung cancer: new chemotherapy combinations.

Over the last decade, we have witnessed improved outcome among patients with non-small cell lung cancer (NSCLC), principally through the use of new and novel treatment programs. A meta-analysis of randomized clinical trials comparing combined chemotherapy and radiation to radiation therapy alone clearly has shown a survival benefit with platinum-based combination chemotherapy administered sequentially or concurrently with thoracic radiation therapy over radiation therapy alone. In addition, combining thoracic radiation therapy with novel drugs or new drug combinations has yielded improvements in median survival duration and long-term survival rates in locally advanced unresectable NSCLC. Paclitaxel and carboplatin are two novel agents that have undergone extensive clinical evaluation at various doses and schedules in combination with thoracic radiation therapy in patients with locally advanced disease. There remains a need, however, for further improvement in metastatic control and prevention of locoregional recurrences. This will likely be achieved through the optimization of chemotherapy regimens to be used in combined modality therapy with thoracic radiation therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Decreased hearing after combined modality therapy for head and neck cancer.

PURPOSE: Combined platinum-based chemoradiation therapy is frequently being used as therapy for head and neck cancer at multiple sites. These therapies are individually ototoxic, but little has been reported on their combined toxicity. MATERIALS AND METHODS: A retrospective investigation of 37 patients known to have undergone therapy with both agents, in combination, for head and neck malignancy was performed. Sixty percent of the patients had complaints of hearing loss subjectively. Reliable pretreatment and posttreatment audiograms were obtained on 15 of these patients. Audiograms were analyzed for sensorineural changes at 0.5, 1, 2, 4, and 8 kHz. RESULTS: By paired t test analysis, there were significant changes in the patients with pretreatment and posttreatment audiograms at all frequencies. More than 50% of the patients had a change of 10 dB or greater in their pure-tone average. More than 85% of the patients experienced changes in their hearing at 4 and 8 kHz. CONCLUSIONS: We conclude that patients undergoing combined modality therapy for head and neck cancer experience hearing loss. We recommend that hearing assessment, including pretreatment and posttreatment audiometry, be performed in all patients undergoing combined platinum-based chemotherapy and radiation for the treatment of head and neck cancer.

Adult↗
PubMed1997

Combined-modality therapy for head and neck cancer.

Chemotherapy, when combined with radiotherapy and/or surgery in the treatment of patients with head and neck cancer, appears to be most efficacious if it is given concurrently with radiotherapy. Concurrent chemotherapy and radiotherapy has been shown to improve locoregional control and/or disease-free or overall survival in some randomized trials. However, acute mucositis is usually increased with simultaneous drug and radiation administration, especially when more than one drug is given concurrently with radiotherapy. The optimal drug or drug combinations for use in combined-modality therapy and the optimal drug and radiation dose schedules remain to be determined. Alternating radiotherapy and combination chemotherapy may also be beneficial and needs further evaluation. Induction chemotherapy followed by definitive radiotherapy in the chemotherapy responders is an alternative treatment option for patients with locally advanced, resectable squamous cell carcinoma of the larynx or hypopharynx who desire organ function preservation. Induction and/or adjuvant chemotherapy may also decrease or delay the appearance of distant metastasis. However, induction chemotherapy has not been shown to improve locoregional control or overall survival. Further clinical trials using novel drugs, innovative radiation and drug dose schedules, and other treatment modifiers are needed to improve the therapeutic ratio.

Chemotherapy, Adjuvant↗
PubMed2002

Histological tumour response to pre-operative combined modality therapy in locally advanced rectal cancer.

BACKGROUND: Pre-operative combined modality therapy (CMT) is used in locally advanced rectal cancer. Its use affects the clinicopathological staging based on the resected specimen. Assessment of the tumour response in the resected specimen may provide prognostic information. This study was undertaken to determine the histological response to pre-operative chemoradiation and to assess the interobserver reliability of a newly developed tumour response grading system for rectal cancer. METHODS: Pre-operative biopsy specimens and the resected specimens of 21 patients with low rectal cancer were assessed. The patients underwent pre-operative CMT consisting of radiotherapy (45 Gy) with 5-FU either as a continuous infusion or as a bolus intravenous infusion with leucovorin. After four to six weeks tumour response was assessed by comparing pre-operative transrectal ultrasound (TRUS) findings (uT1-4, uN0-1) with postoperative histopathological assessment (pT1-4, pN0-1) using UICC TNM characteristics. Tumour response was defined as a decrease in T status. The histological response to CMT was based on the tumour regression grade (TRG) and ranged from fibrosis extending through the rectal wall with no residual cancer (TRG 1), to no evidence of tumour response (TRG 5). Inter-observer reliability was assessed using weighted and unweighted kappa statistics. RESULTS: Local downstaging was demonstrated in 11/21 (52%) of patients. Three of 21 patients had a TRG 1 response. Thirteen of 21 (62%) patients had TRG 1-3 responses to CMT. There was no significant correlation between local downstaging and TRG. The interobserver correlation coefficient for assessment of TRG was 0.88 (unweighted kappa). CONCLUSIONS: Local downstaging by pre-operative CMT can be demonstrated if pre-operative TRUS staging is compared to standard pathology staging in patients with rectal cancer. Local downstaging is not directly related to histologic response as assessed by TRG. Inter-observer reporting of tumour regression grade (TRG) is reliable.

Journal Article↗
PubMed1992

Combined modality therapy for small cell lung cancer.

Small cell carcinoma is one of the solid cancers for which chemotherapy is effective and can prolong the survival of patients. There is a general agreement that the standard regimen is PVP (cisplatin/etoposide) or alternating PVP-CAV (cyclophosphamide/doxorubicin/vincristine) therapy, replacing CAV, which had been considered standard. For the improvement of the treatment results of small cell carcinoma combined modality therapy including radiotherapy and/or surgery is essential, especially against limited disease. The effect of prophylactic cranial irradiation is obscure, because of the relapse to other sites of organs and the late complications of brain radiation. The present status of combined modality therapy for small cell carcinoma is reviewed and the future essential trials are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Is combined modality therapy necessary for advanced Hodgkin's disease?

PURPOSE: To determine whether single-modality therapy is optimal management for patients with Stage III-IV Hodgkin's disease. METHODS AND MATERIALS: All patients with advanced (Stage III and IV) Hodgkin's disease treated at the University of Florida from 1964 through 1989 (n = 141) were studied retrospectively for factors predictive of good outcome with single-modality therapy. Treatment modalities varied and were distributed as follows: combined-modality therapy (CMT), 55 patients; chemotherapy alone (CX), 50 patients; and radiotherapy alone (RT), 36 patients. RESULTS: Ten-year rates of freedom from relapse and overall survival for all Stage III patients were 66% and 59% compared with 36% and 35% for Stage IV patients. The RT subset was highly selected with the majority of patients having nonbulky Stage IIIA disease. Within the RT group, multivariate analysis identified the degree of splenic involvement and age as the factors most associated with freedom from relapse. In patients treated with CX, multivariate analysis identified bulky tumor (maximum transverse tumor dimension > 6 cm) as the most important prognostic factor for relapse. In patients without bulky disease (< or = 6 cm), the probabilities of freedom from relapse and overall survival at 10 years, respectively, according to treatment group were 53% and 58% for RT patients, 60% and 56% for CX patients, and 83% and 71% for CMT patients. For patients without bulky disease, the probability of freedom from relapse was significantly better for the CMT group than for CX patients (p = 0.03) or RT patients (p = 0.04), but there was no statistical difference in overall survival among the three groups. In patients with bulky disease (> 6 cm), the probabilities of freedom from relapse and overall survival at 10 years were 44% and 45% for RT patients, 9% and 0% for CX patients, and 72% and 58% for CMT patients. Freedom from relapse and overall survival were significantly better (p = 0.0001) for CMT patients compared with CX patients. Fatal hematopoietic disorders developed in 10 patients: 2 of 36 RT patients, 2 of 50 CX patients, and 6 of 55 CMT patients. Nine patients had received chemotherapy, and eight had six or more cycles of alkylator-based chemotherapy. CONCLUSION: This retrospective study suggests that combined-modality therapy is preferable to single-modality therapy in the majority of patients with advanced Hodgkin's disease.

Adolescent↗