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M S Kies

Publications and source records attributed to M S Kies.

At least 19 recordsLinked to original sources
PubMed2004

A phase I/II trial of induction chemotherapy with carboplatin and gemcitabine followed by concurrent vinorelbine and paclitaxel with chest radiation in patients with stage III non-small cell lung cancer.

PURPOSE: We designed a phase I/II trial in order to evaluate the efficacy and tolerability of induction carboplatin and gemcitabine and the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of subsequent chemoradiotherapy with weekly vinorelbine and paclitaxel in patients with stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients had pathologically confirmed N2-N3 stage NSCLC, adequate end-organ function, and ECOG performance status 0-2. Carboplatin was administered at an AUC of 5 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days, for two cycles, followed by weekly vinorelbine 10-15 mg/m2 and paclitaxel 50 mg/m2 and conventional chest radiotherapy up to 66 Gy. Patients with resectable disease underwent thoracotomy after 40-45 Gy. RESULTS: Thirty-nine eligible patients were enrolled; 17 had stage IIIB NSCLC. Grade 3 esophagitis developed in 4/5 patients on the second dose level of chemoradiotherapy (i.e. vinorelbine 15 mg/m2) and was considered dose-limiting. Of 34 patients treated at the maximum tolerated dose (i.e. vinorelbine 10 mg/m2), 2 patients (6%) had pneumonitis >grade 2 and 3 (9%), esophagitis >grade 2. Induction chemotherapy was well tolerated with only one patient developing >grade 2 non-hematologic toxicity (nausea). Forty-one percent of patients had an objective response after induction chemotherapy and 51% after chemoradiotherapy. Nineteen patients, 16 of whom had stage IIIA, underwent surgical resection. The pathologic complete response rate was 16% (42% in the mediastinal lymph nodes). With a median follow-up of 31 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 23 and 34%, respectively, and the median OS was 25 months. CONCLUSIONS: We identified a well-tolerated and active chemoradiotherapy regimen. Survival results are promising and the addition of a biologic agent to this regimen is of interest.

Adult↗
PubMed2004

Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: a 9-year, 337-patient, multi-institutional experience.

BACKGROUND: Locoregionally advanced, stage IV head and neck cancer has traditionally carried a poor prognosis. We sought to assess changes in patterns of failure, prognostic factors for recurrence, and overall outcome, using two different strategies of chemoradiotherapy conducted in prospective, multi-institutional phase II trials. PATIENTS AND METHODS: Three hundred and thirty-seven stage IV patients were treated from 1989 to 1998. We compared locoregional and distant recurrence rates, overall survival and progression-free survival from two different treatment strategies: intensive induction chemotherapy followed by split-course chemoradiotherapy (type 1, n=127), or intensified, split-course, hyperfractionated multiagent chemoradiotherapy alone (type 2, n=210). Univariate and multivariate analyses of 12 chosen covariates were assessed separately for the two study types. RESULTS: The pattern of failure varied greatly between study types 1 and 2 (5-year locoregional failure of 31% and 17% for study types 1 and 2, respectively, P=0.01; 5-year distant failure rate of 13% and 22% for study types 1 and 2, P=0.03). Combined 5-year overall survival was 47% [95% confidence interval (CI) 41% to 53%) and progression-free survival was 60% (95% CI 55% to 66%). Both treatment strategies yielded similar survival rates. Poor overall survival and distant recurrence were best predicted by advanced nodal stage. Locoregional recurrence was extremely rare for patients with T0-T3 tumor stage, regardless of lymph-node stage. CONCLUSIONS: This analysis suggests that pattern of failure in primary head and neck cancer may be dependent upon treatment strategy. Randomized clinical trials of induction chemotherapy are warranted as a means to determine if a decrease in distant metastases can lead to an increase in survival rates in the setting of effective chemoradiotherapy for locoregional control. Additionally, this analysis provides impetus for randomized clinical trials of organ preservation chemoradiotherapy in sites outside the larynx and hypopharynx.

Adult↗
PubMed2003

Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal cancer.

BACKGROUND: Since 1990, we have treated patients with advanced nasopharyngeal cancer with induction chemotherapy and concomitant chemoradiotherapy. We herein report the results of our experience. PATIENTS AND METHODS: From 1990 to 1999, 27 patients with locoregionally advanced nasopharyngeal cancer were treated with induction chemotherapy followed by concomitant chemoradiotherapy. Using the American Joint Committee on Cancer's 1992 stage classification, all patients were stage III (11%) or IV (89%). By histology, 63% were poorly differentiated carcinoma and 37% squamous cell carcinoma. The median age was 42 years. Three cycles of induction chemotherapy consisting of cisplatin, 5-fluorouracil, leucovorin and interferon-alpha2b were administered, followed by concomitant chemoradiotherapy consisting of seven cycles of 5-fluorouracil, hydroxyurea and once-daily radiotherapy (FHX) on a week-on week-off schedule. The median radiotherapy dose was 70 Gy. RESULTS: Clinical response to induction chemotherapy was 100%, 54.2% complete response (CR) and 45.8% partial response. Clinical and/or pathological (37% of all patients had post-treatment biopsy with or without neck dissection) CR after FHX was 100%. At a median follow-up of 52 months, three failures were observed. Two patients have died of disease, one of local failure and one of distant metastases. One patient is alive with an isolated rib metastasis. At 5 years, actuarial locoregional control is 93% and actuarial distant control 92%. The overall survival at 3 and 5 years is 88% and 77%, respectively. Four patients died of unrelated illnesses and had no evidence of disease with respect to their nasopharyngeal cancer. The progression-free survival at 3 and 5 years is 92% and 86%, respectively. Thirty-three per cent of patients required a reduction in the chemotherapy dose due to acute toxicity. Chronic toxicity was not observed, with all patients able to eat orally without dietary restrictions. CONCLUSIONS: Treatment of locoregionally advanced nasopharyngeal cancer with induction chemotherapy followed by concomitant chemoradiotherapy resulted in excellent overall survival with acceptable toxicity. These results are encouraging and warrant further investigation of intensified approaches.

Adult↗
PubMed2003

Concurrent chemoradiotherapy for N2 or N3 squamous cell carcinoma of the head and neck from an occult primary.

BACKGROUND: Our aim was to explore the use of concurrent chemoradiotherapy in the management of patients with squamous cell carcinoma of the head and neck from an occult primary (HNCOP). PATIENTS AND METHODS: From 1991 to 2000, 25 patients with T0N2M0 or T0N3M0 HNCOP were entered into five sequential phase II clinical trials. Chemoradiotherapy consisted of a split course of radiotherapy with concurrent 5-fluorouracil and hydroxyurea either alone or with cisplatin, or paclitaxel. Two of the five protocols incorporated induction chemotherapy. RESULTS: Nodal stage was N2a in five patients (20%), N2b in 13 (52%), N2c in one (4%) and N3 in six (24%). Twenty-two patients (88%) underwent neck dissection; 14 of 22 patients underwent neck dissection before initiating protocol therapy. Total radiation doses of 55-75 Gy (median 60 Gy) were delivered; radiation fields included the potential sites of mucosal primaries and the neck bilaterally. Selected patients received a radiation boost to the involved neck. With a median follow-up of 3.9 years, three patients have progressed (one local, two distant) and seven patients have died. Deaths were due to disease progression (three) or unrelated causes (four). No metachronous primaries developed. The 5-year progression-free and overall survival was 87% and 75%, respectively. CONCLUSION: Combined-modality treatment with intensive chemoradiotherapy results in excellent disease control and long-term survival for patients with N2-N3 HNCOP and compares favorably with traditional therapy.

Adolescent↗
PubMed2001

Concomitant infusional paclitaxel and fluorouracil, oral hydroxyurea, and hyperfractionated radiation for locally advanced squamous head and neck cancer.

PURPOSE: To improve local disease control and survival with organ preservation, we conducted a phase II multi-institutional trial with a concomitant taxane-based chemotherapy and hyperfractionated radiation regimen. PATIENTS AND METHODS: Sixty-four patients with locally advanced squamous cancers (stage IV, 98%; N2/3, 81%) were treated on an intensive regimen consisting of 5-day (120-hour) infusions of paclitaxel (20 mg/m(2)/d) and fluorouracil (600 mg/m(2)/d), oral hydroxyurea 500 mg every 12 hours for 11 doses, and radiation 1.5 Gy bid (T-FH2X). Chemoradiation was administered concomitantly on days 1 to 5 of each 14-day cycle. A full treatment course consisted of five cycles during a 10-week period to a total radiation dose of 72 to 75 Gy. RESULTS: The median follow-up for the group is 34 months. At 3 years, progression-free survival is 63%, locoregional control is 86%, and systemic control is 79%; overall survival is 60%. Seventeen patients died of recurrent cancer, two died of second primary cancers, and four died of other causes. Side effects observed include anemia (22% required transfusion), leucopenia (34%, grade 3 to 4), and mucositis (84%, grade 3 to 4). Organ preservation principles were maintained. At 1 year posttreatment, 61% of patients had severe xerostomia and 47% had compromised swallowing. There was little disturbance of speech quality in 97% of patients at the same follow-up point. CONCLUSION: T-FH2X is a highly active and tolerable concomitant chemotherapy and hyperfractionated radiation regimen that induces sustained local tumor control and holds promise for improved survival with organ preservation in high-risk patients. Identification of less toxic therapy and improved distant disease control are needed. T-FH2X should be tested in a randomized trial and compared with a less intensive concomitant regimen that uses once-daily radiation fractionation.

Administration, Oral↗
PubMed2001

Locally advanced head and neck cancer.

The simultaneous administration of chemotherapy and radiation has produced a significant impact on the treatment of advanced squamous cell carcinomas of the head and neck. Although no single regimen has emerged as the "standard" approach, recent trials have consistently demonstrated the superiority of combined treatment programs over radiotherapy alone for local tumor control and overall survival. Moreover, multimodal treatment has emerged with important ancillary goals of organ preservation, improved cosmesis, and enhancement of quality of life. With improving survival in all stages of disease, much attention can be given to identifying effective measures to reduce the risk of metachronous primary cancers in this high-risk group.

Antineoplastic Agents↗
PubMed2001

Chemotherapy for skull base cancers.

This article focuses on treatment options for select skull base problems that have decreased post-treatment morbidity and, in many cases, improved survival. The select skull base cancers covered include nasopharyngeal carcinoma, squamous cell carcinoma of the paranasal sinuses, sinonasal undifferentiated carcinoma, neuroendocrine carcinoma, esthesioneuroblastoma, and salivary gland carcinoma.

Carcinoma, Adenoid Cystic↗
PubMed2001

Sequential induction chemotherapy and concomitant chemoradiotherapy in the management of locoregionally advanced laryngeal cancer.

PURPOSE: To determine overall survival, progression-free survival, rate of voice preservation, and patterns of failure in locoregionally advanced laryngeal cancer treated with induction chemotherapy with or without surgery followed by concomitant chemoradiation. BACKGROUND: Locoregionally advanced laryngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and clinical and functional outcomes have been poor. Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent randomized head and neck trials. PATIENTS AND METHODS: Advanced head and neck cancer patients were enrolled onto two consecutive phase II studies. Induction treatment consisted of three cycles of cisplatin, 5-fluorouracil (5-FU), leucovorin, and interferon-alpha 2b (PFL-IFN) followed by surgery for residual disease. Surgical intent was to spare the larynx when possible. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-FU, hydroxyurea, and a planned total radiotherapy dose of 7000 cGy (FHX). RESULTS: A subset of thirty-two laryngeal cancer patients with predominantly stage IV disease comprises the study group for this report. Clinical CR was observed in 59% of patients following induction therapy. The median follow-up was 63.0 months for surviving patients and 44.5 months for all patients. At five years, overall survival is 47%, progression-free survival is 78%, and locoregional control is 78%. No distant failures were observed. Voice preservation with disease control was 75% at five years. Only two total laryngectomies were performed during the course of treatment and follow-up. Treatment-related toxicity accounted for two deaths. CONCLUSIONS: The addition of concomitant chemoradiotherapy to induction chemotherapy for locoregionally advanced laryngeal cancer appears to increase locoregional control and survival rates. PFL-IFN-FHX resulted in high rates of disease cure and voice preservation in a group of patients that has traditionally fared poorly in both clinical and functional outcome.

Aged↗
PubMed2001

Squamous cell carcinoma of the head and neck in nonsmokers: clinical and biologic characteristics and implications for management.

Squamous cell carcinoma of the head and neck has been strongly linked to chronic tobacco and alcohol abuse. However, we are increasingly recognizing subgroups of patients without traditional risk factors. Recent clinical and molecular investigations suggest that there are distinctive clinical entities, particularly affecting young patients with cancers of the oral tongue and oropharynx. We review data from clinical observations and current biologic inquiries and consider therapeutic implications for these important patient subgroups.

Adult↗
PubMed2001

ZD1839 (Iressa) in non-small-cell lung cancer.

The epidermal growth factor receptor (EGFR) signaling pathway plays an important role in a number of processes that are key to tumor progression, including cell proliferation, angiogenesis, metastatic spread, and inhibition of apoptosis. EGFR is expressed or overexpressed in non-small-cell lung cancer (NSCLC), and EGFR-mediated growth has been associated with advanced disease and poor prognosis in NSCLC patients. ZD1839 (Iressa) is an orally active, selective EGFR-tyrosine kinase inhibitor that blocks EGFR signal transduction. In preclinical studies using NSCLC cell lines, ZD1839 has been shown to inhibit tumor cell growth. In addition, ZD1839, as monotherapy and in combination with commonly used cytotoxic agents, has produced growth delay in NSCLC human xenografts. Preliminary results from phase I trials in patients with advanced disease have shown that ZD1839 has excellent bioavailability, an acceptable tolerability profile, and promising clinical activity in patients with a variety of tumor types, particularly in NSCLC. ZD1839 is currently in phase III clinical development for the treatment of advanced NSCLC.

Journal Article↗
PubMed2000

The role of cervical lymphadenectomy after aggressive concomitant chemoradiotherapy: the feasibility of selective neck dissection.

OBJECTIVES: To evaluate the necessity, technical feasibility, and complication rate of neck dissection performed on patients with head and neck cancer after 5 cycles of concomitant chemoradiotherapy (CRT) and to justify a selective neck dissection (SND) approach and define the optimal timing of post-CRT neck dissection. DESIGN AND SETTING: Retrospective analysis in an academic university medical center. PATIENTS: Sixty-nine eligible patients with advanced (stage III and IV) head and neck cancer who have undergone 1 of 4 CRT protocols. Patients ranged in age from 36 to 75 years, and surgical procedures were performed over a 4-year period. Follow-up ranged from 6 to 64 months. INTERVENTION: Neck dissection (most commonly unilateral SND) performed within 5 to 17 weeks after CRT completion. MAIN OUTCOME MEASURES: Complication rate and incidence of positive pathology (viable cancer) in pathologic neck dissection specimens. RESULTS: Seven (10%) of 69 patients developed wound healing complications, 4 (6%) of whom required surgical intervention for ultimate closure. There were no wound infections. Other complications occurred in 11 (16%) of 69 patients and included need for tracheotomy, nerve transection and paresis, and permanent hypocalcemia. Twenty-four (35%) of 69 patients revealed microscopic residual disease. Ten (50%) of 20 patients with N3 neck disease had positive pathology, whereas 14 (36%) of 39 patients with N2 disease had viable carcinoma in the dissection specimen (P =.09 by chi(2) analysis). There was no significant relation between radiologic complete response or partial response and residual microscopic cancer. In 1 patient, disease recurred in the neck after dissection. Mean follow-up time was 30.3 months. CONCLUSIONS: (1) Neck dissection for patients with N2 or greater neck disease after CRT is necessary to eradicate residual disease. (2) The complication rate of SND after CRT with hyperfractionated radiotherapy is low. (3) SNDs are technically feasible when performed within the "window" between the acute and chronic CRT injury (4-12 weeks). (4) SNDs, rather than more radical procedures, appear to be therapeutically appropriate in this group of patients because of the low incidence of disease recurrence in the neck.

Adult↗
PubMed2000

Overexpression of p53 in squamous cell carcinoma of the tongue in young patients with no known risk factors is not associated with mutations in exons 5-9.

BACKGROUND: This study investigated the status of the p53 tumor suppressor gene in patients less than 40 years of age who had squamous cell carcinoma of the tongue develop with no known risk factors. METHODS: Histologic sections from 21 patients were prepared from formalin-fixed, paraffin-embedded tissue and were processed for standard immunohistochemistry for detection of the p53 protein. In addition, tumors were evaluated by single-strand conformation polymorphism and by DNA sequencing to identify potential mutations in the conserved exons (5-9) of the p53 gene. RESULTS: Eighty-one percent (17 of 21) of the patients overexpressed p53 by immunohistochemical analysis. However, none of these patients demonstrated mutations in exons 5-9 of the gene. CONCLUSIONS: These data suggest that the molecular mechanisms by which the young individuals with no risk factors had altered p53 function in oral squamous cell carcinoma may differ from those of the more typical population of individuals who have this malignancy develop.

Adolescent↗
PubMed2000

Phase II pilot study of combined chemohormonal therapy with doxorubicin and estramustine in metastatic prostate cancer.

Twenty-nine patients with progressive hormone-refractory metastatic adenocarcinoma of the prostate were treated with daily estramustine phosphate at 10 mg/kg, and I.V. doxorubicin 50 mg/m2 every 3 weeks. Twenty-six patients were evaluable. Four of seven patients with nonosseous measurable disease had partial responses lasting 3 to 10 months. Eleven of 19 patients with osseous metastases had stable disease or improvement on bone scan, 6 of these for 7 months or longer. Median time to progression was 20 weeks, and the median survival was 43 weeks.

Adenocarcinoma↗
PubMed2000

Concomitant chemoradiotherapy as primary therapy for locoregionally advanced head and neck cancer.

PURPOSE: To achieve locoregional control of head and neck cancer, survival, and organ preservation using intensive concomitant chemoradiotherapy. PATIENTS AND METHODS: This study was a phase II trial of chemoradiotherapy with cisplatin 100 mg/m(2) every 28 days, infusional fluorouracil 800 mg/m(2)/d for 5 days, hydroxyurea 1 g orally every 12 hours for 11 doses, and radiotherapy twice daily at 1.5 Gy/fraction on days 1 through 5 (total dose, 15 Gy). Five days of treatment were followed by 9 days of rest, during which time patients received granulocyte colony-stimulating factor. Five cycles (three with cisplatin) were administered over 10 weeks (total radiotherapy dose, </= 75 Gy). Adjuvant chemoprevention with retinoic acid and interferon alfa-2A was offered. RESULTS: Seventy-six patients were treated (stage IV, 93%; N2, 54%; N3, 21%). At a median follow-up of 38 months, the 3-year progression-free survival is 72%, locoregional control 92%, systemic control 83%, and overall survival 55%. Toxicities included mucositis (grade 3, 45%; grade 4, 12%), neutropenia (grade 4, 39%), and thrombocytopenia (grade 4, 53%). Surgery at the primary site was performed in 13 patients, and 39 had neck dissection. A majority of patients declined adjuvant chemoprevention. Pharmacokinetic parameters were not prognostic of tumor control. Quality of life declined during treatment but returned from good to excellent by 12 months after treatment. CONCLUSION: Intensive concomitant chemoradiotherapy leads to high locoregional control and survival rates with organ preservation and a reversal of the historical pattern of failure (distant > locoregional). Surgery after concomitant chemoradiotherapy is feasible. Compliance with adjuvant chemoprevention is poor. Identification of less toxic regimens and improved distant disease control emerge as important future research goals.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

The use of concurrent chemotherapy and radiotherapy for locoregionally advanced head and neck cancer.

The long-term prognosis of patients with advanced head and neck cancer has been poor. Combined modality approaches, such as induction chemotherapy, adjuvant chemotherapy, and concomitant chemoradiotherapy, have been studied in an effort to control local tumor and reduce systemic tumor dissemination. Randomized clinical trials and meta-analyses have both demonstrated a survival benefit with concomitant chemoradiotherapy, despite the omission of surgery. Because of both direct and indirect toxicities of concomitant chemoradiotherapy, less-toxic and equally effective strategies are being investigated. Concurrent chemoradiotherapy should be considered a possible standard therapy option for head and neck cancer patients and should be administered at treatment centers with experienced health care providers who have access to clinical trials.

Combined Modality Therapy↗
PubMed1998

Induction chemotherapy followed by concurrent chemoradiation for advanced head and neck cancer: improved disease control and survival.

PURPOSE: To determine tumor response rate, patterns of failure, toxicity, and survival in advanced squamous head and neck cancer after a combined treatment program that consists of induction chemotherapy, organ-sparing surgery, and concurrent chemoradiation. Long-term outcome data are presented. PATIENTS AND METHODS: Between July 1991 and March 1993, 93 patients received three cycles of induction chemotherapy that consisted of cisplatin, fluorouracil (5-FU), l-leucovorin, and alpha-interferon2b (PFLl-alpha) followed by optional limited surgery and six to eight cycles of 5-FU, hydroxyurea, and concurrent radiation (FHX) to a total radiation dose of 65 to 75 Gy. RESULTS: Ninety-three patients were entered onto this study and 97% had stage IV disease, with 66 patients who were N2 or N3. Sixty-one patients (66%) achieved a clinical complete remission (CR) after induction therapy. Thirty-four patients underwent surgery. Seventy-nine patients proceeded to FHX. With a median follow-up time of 43 months for surviving patients, 20 patients have had disease progression (13 local, two distant, five both), and there have been 35 deaths (18 from disease, six treatment-related, two from a second primary, and nine for other medical reasons). At 5 years, progression-free survival is 68%, and overall survival is 62%. Surgery was organ-preserving, as only a single laryngectomy and no glossectomies were performed in primary management. Acute toxicity related to PFLl-alpha consisted of severe or life-threatening mucositis in 57% and leucopenia in 65% of patients. During FHX, 81% of patients had grade 3 or 4 mucositis. CONCLUSION: PFLl-alpha is a highly active regimen that induced clinical CR in two thirds of patients. When followed by limited surgery and FHX, resultant local and distant disease control, organ preservation, and overall 5-year survival are very promising in high-risk stage IV patients. Based on these local control and survival data, further evaluation of this treatment sequence, induction chemotherapy followed by concurrent chemoradiation, is warranted. Identification of similarly active but less toxic regimens is a high priority.

Adolescent↗
PubMed1997

Phase II study of induction and adjuvant chemotherapy for squamous cell carcinoma of the head and neck. A long-term analysis for the Illinois Cancer Center.

BACKGROUND: In 1982, the Illinois Cancer Center initiated a Phase II trial in which the following treatment was administered: Induction chemotherapy (cisplatin and infusional 5-fluorouracil [5-FU]) was administered before definitive local therapy. Definitive local therapy, consisting of surgery, radiation, or both, was followed by three cycles of the same chemotherapy program. METHODS: Eligible patients had Stage III or IV squamous cell carcinoma of the head and neck with no distant metastases. Three cycles of induction chemotherapy were given. Cisplatin, 100 mg/m2, was infused over 60 minutes on Day 1; thereafter, 5-FU (1000 mg/m2/day) was given continuously for 5 days. Cycles were repeated at 3-week intervals. Local therapy was individualized, according to tumor stage and site. Patients who responded were to receive an additional three cycles of chemotherapy after surgery or radiation. RESULTS: Eighty-one patients were entered into the trial, and 71 were considered both eligible and evaluable. After induction chemotherapy, 59 patients (83%) responded, 23 of whom experienced complete response. Sixty-nine patients completed definitive local treatment, but only 22 proceeded to the planned adjuvant cycles of treatment. Median follow-up of surviving patients was 12 years. At last follow-up, 13 patients were alive and free of malignancy, 9 of whom never had disease recurrence or a second primary tumor. These 13 patients had an acceptable quality of life, were ambulating, and were fully capable of caring for themselves. Overall, nine patients had second primary malignancies. Thirty-four percent of patients were alive at 5 years, and 21% were alive at 10 years. Of 58 deaths, 44 resulted from progressive disease and 8 resulted from second primary cancers. Four patients died of unrelated causes, and two suffered lethal acute toxicity from the chemotherapy program. Late toxicity was moderate. Among 23 patients surviving at least 6 years, there were 3 cases of hypothyroidism, presumed to be secondary to radiation. Xerostomia was modest, consistent with usual radiation effects. Of the 13 patients who were alive and free of malignancy at last follow-up, none had clinical manifestations of serious late end organ toxicity. CONCLUSIONS: During long term follow-up after multimodal treatment of locally advanced squamous cell carcinoma, no obvious benefit was observed from the chemotherapy component of the treatment regimens rendered. Only 21% of patients achieved 10-year survival with the following causes of failure, in descending order of frequency: disease recurrence, second malignancies, other medical problems, and treatment-related deaths. The results of this trial are consistent with the results of other induction chemotherapy trials, indicating the need for innovative treatment strategies. These data do not support the continued use of induction chemotherapy with the cisplatin and infusional 5-FU program.

Adult↗