PubMed HealthSearch

Biomedical subjects

W R Panje

Publications and source records attributed to W R Panje.

At least 19 recordsLinked to original sources

Favorable long-term survival following induction chemotherapy with cisplatin, fluorouracil, and leucovorin and concomitant chemoradiotherapy for locally advanced head and neck cancer.

BACKGROUND: The majority of patients with head and neck cancer die of locoregional recurrence of disease following surgery and/or radiotherapy. PURPOSE: Our purpose was to administer induction chemotherapy, perform surgery, and administer concomitant chemoradiotherapy in rapid sequence and to evaluate their impact on locoregional and distant tumor control. METHODS: Sixty-four patients with previously untreated, locoregionally advanced head and neck cancer received two cycles of cisplatin, bleomycin, and methotrexate (PBM) (33 patients) or cisplatin, fluorouracil (5-FU), and leucovorin (PFL) (31 patients). PFL was given to patients who were unable to receive bleomycin. Local therapy consisted of surgery and/or concomitant chemoradiotherapy with 5-FU, hydroxyurea, leucovorin, and radiotherapy (FHX-L), all administered every other week. RESULTS: Complete and overall induction response rates were 21% and 79%, respectively, for PBM and 29% and 81%, respectively, for PFL. At completion of local therapy, 81% of the patients were disease-free. With a median follow-up of 35 months, the median survival and time to progression are 22 and 17 months, respectively, for PBM and have not been reached for PFL. Locoregional recurrence of disease is 30% for PBM and 26% for PFL. Distant disease progression is 24% for PBM and only 3% for PFL. CONCLUSIONS: The sequencing of induction chemotherapy and concomitant chemoradiotherapy is feasible and results in a high local control rate and in an encouraging survival rate with PFL. The high distant failure (i.e., outside the head and neck area) rate of PBM suggests insufficient systemic activity for that regimen. IMPLICATIONS: Concomitant FHX-L chemoradiotherapy may improve regional control rates of advanced head and neck cancer. Effective systemic therapy may be needed to control systemic micrometastases. PFL, but not PBM, appears to be suitable to accomplish that goal.

Antineoplastic Combined Chemotherapy Protocols

Rounded atelectasis.

Explore the source record for details and available documents.

Carcinoma, Squamous Cell

Concomitant chemoradiotherapy with cisplatin, 5-fluorouracil and hydroxyurea in poor-prognosis head and neck cancer.

Based on encouraging results with 5-fluorouracil (5-FU), hydroxyurea, and concomitant radiotherapy in patients with advanced or recurrent head and neck cancer, an attempt was made to modulate the regimen by the addition of cisplatin as a third active agent. A cohort of 26 patients with head and neck cancer of all histologies were entered into a broad phase I study investigating simultaneous radiation therapy, 5-FU (with or without leucovorin), HU, and infusional cisplatin administered on an alternate-week schedule. Eleven patients (group 1) had failed prior curative local therapy and 15 patients (group 2) were considered to have a poor prognosis with standard therapy. The median follow-up was 30 months. The response rate for all evaluable patients was 82% (14/17), and the complete response rate was 65% (11/17). Patients in group 1 demonstrated a high failure rate (9/11), while few group 2 patients failed after treatment (2/15). The median time to progression was 4.4 months in group 1 and has not been reached in group 2. Patients in group 1 failed locally (7/11), while no local failures were observed in group 2. Acute and cumulative hematologic toxicity was encountered at all dose levels and schedules tested and prevented escalation of the cisplatin dose beyond the desired level of 100 mg/m2 per months. Mucositis was a second significant toxicity in patients with head and neck cancer and was more pronounced during cycles containing leucovorin. A detailed analysis of survival, time to progression, and site of failure is presented.

Adult

Perspectives on combination chemotherapy with concomitant radiotherapy for poor-prognosis head and neck cancer.

Concomitant chemoradiotherapy has resulted in small increases in disease-free or overall survival for patients with advanced head and neck cancer when single-agent chemotherapy is used. To increase the efficacy of this approach, combination chemotherapy also has been explored. In this setting, acute toxicities are frequently increased, necessitating interruption or protraction of radiotherapy. Despite this fact, pilot trials using 5-fluorouracil-based chemotherapy have indicated high response and encouraging survival rates. Some of these trials will be reviewed, with a focus on studies with 5-fluorouracil, hydroxyurea, and cisplatin conducted at the University of Chicago.

Adult

Hydroxyurea with concomitant radiotherapy for locally advanced head and neck cancer.

Hydroxyurea is an active single agent in squamous cell cancer of the head and neck. It has been used clinically, most frequently as a radiation-enhancing agent with concomitant radiotherapy. Pilot trials testing hydroxyurea in this setting reported encouraging results. Two randomized trials have been conducted with inconclusive results, possibly relating to study cohort size and short period of follow-up. More recently, hydroxyurea has been investigated with 5-fluorouracil and concomitant radiotherapy. A sound theoretic rationale can be made for this approach and data derived from a phase I/II study are presented. These support the further investigation of this regimen.

Administration, Oral

Survival and analysis of failure following hydroxyurea, 5-fluorouracil and concomitant radiation therapy in poor prognosis head and neck cancer.

Thirty-nine patients with head and neck cancer were entered into Phase I-II study of simultaneous radiation therapy with continuous infusion fluorouracil at 800 mg/m2/day and escalating doses of hydroxyurea. Twenty of these patients had recurrent disease after previous surgery and/or radiation therapy (group 1). Nineteen patients had not received prior local therapy but had advanced-stage disease (group 2). Cycles were repeated every other week until the completion of radiation therapy. The median follow-up was 32 months. Patients with recurrent disease were generally treated with palliative doses of radiation (median dose 5,000 cGy) while previously untreated patients received radiation with curative intent (median dose 7,040 cGy). The response rate for 15 evaluable patients with recurrent disease was 93% with 40% of patients achieving a complete response. For 17 evaluable patients without recurrent disease the response rate was 100%, with a complete response rate of 71%. This regimen exhibited a high activity and significant palliative benefit in group 1 patients. However the local control rate was 25% (5/20) because the majority of patients in this group eventually developed a local recurrence. The local control rate for group 2 patients was 84% (16/19). The higher local failure rate in group 1 patients appeared to be attributable to the palliative doses of radiation delivered and the fewer cycles of treatment received. We conclude that this regimen has palliative benefit in patients who have failed prior local therapy and has the potential for cure in patients with poor prognosis advanced stage disease as well.

Adult

Head and neck cancer: an analysis of the incidence, patterns of treatment, and survival at the University of Iowa.

A retrospective study was performed with use of tumor registry data to evaluate tumor population characteristics, the patterns of care, and patient survival in 4,506 patients with head and neck cancers seen at The University of Iowa Hospitals and Clinics between 1960 and 1985. The total number of patients with head and neck cancers seen per year and the distribution by anatomic site remained relatively stable over the 26-year period. However, there was a general trend toward more advanced stages in later years. The selection of a treatment modality for this patient population correlated well with the site and stage of the disease and with the treatment philosophy of the managing physicians. Patient survival rates correlated well with the site and stage of the disease. There was a gradual improvement in 5-year survival rates over the 26-year period, from approximately 39% in 1960 to approximately 47% in 1984. This was principally due to an improvement in the 5-year survival rate for patients with "regional stage" disease, from approximately 22% in 1960 to approximately 41% in 1985.

Combined Modality Therapy

Prognostic factors in advanced head and neck cancer patients undergoing multimodality therapy.

A retrospective analysis was performed to investigate potential prognostic factors for complete remission to neoadjuvant chemotherapy and overall survival in patients with previously untreated stage III and stage IV head and neck cancer. Eighty consecutive patients were treated in one of two studies investigating three or four courses of neoadjuvant chemotherapy. Before local therapy and surgery and/or radiotherapy, 29% attained a complete remission. No strong significant and independent predictor of complete remission was identified. Only nodal stage (N) was found moderately associated with complete remission (p = 0.06). Node-negative patients had higher remission rates. Less important predictors were tumor stage (T) and site of disease; nasopharyngeal patients had superior remission rates (56%). With a median followup of 45 months and estimated 3-year survival rate of 38% (median 23.7 months), individual factors predictive of survival included pretherapy weight loss, performance status, alcohol use, pretherapy serum albumin level, site of disease, and N stage. In multivariate testing weight loss was identified as the strongest independent predictor of survival (p less than 0.0001) and surpassed other health status measures, such as performance status and serum albumin level. In addition, N stage (p = 0.019) and alcohol use (p = 0.017) were found to be predictive. A cross-classification by N stage and weight loss revealed risk groups with distinctly different prognoses, which may be useful for design and analysis in future trials.

Adolescent

Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution.

Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy. Twenty-two patients (43%) had a clinical CR that was pathologically confirmed in 12 patients (24%), and 24 patients (47%) had a PR for an overall response rate of 90%. Local therapy included surgery in 24 patients (47%) and radiotherapy alone in 22 patients (43%). Adjuvant chemotherapy was administered to 32 patients (63%) frequently at great dose reduction. At a median follow-up of 90 months, the median survival is 22 months (95% confidence interval, 15 to 36 months), and the 5-year survival is 25%, with only five patients known to be alive and disease-free at this time. The median time to progression is 14 months, with 29 patients (57%) having documented progression of their head and neck cancer and eight (16%) having progression of a second neoplasm. Seven patients died of intervening medical events. This high incidence of second malignancies supports the continued investigation of chemoprevention for patients in CR. Despite the known high response rates achieved with cisplatin and 5-FU induction chemotherapy, the overall poor survival data reported here should lead to a thorough reexamination of the frequent administration of this regimen in the community.

Adolescent

New concepts in head and neck surgery.

New methods in head and neck cancer treatment have enabled the oncologic surgeon to pursue the goals of conservation of head and neck physiologic function, reduce the morbidity and mortality associated with advanced head and neck cancers, and increase the cure rates for cancers once considered inoperable. Advances in multimodality therapy may lead in the next decade to less surgical mutilation and higher cure rates.

Carcinoma, Squamous Cell

The temporoparietal fascia flap in head and neck reconstruction.

The temporoparietal-galeal system of flaps provides the head and neck surgeon with a reliable source of pliable, well vascularized local tissue capable of reconstructing auricular, oropharyngeal/base of tongue/lateral floor of mouth, dural, mandibular, and facial defects. This report provides a description of the types of flaps available, methods of dissection, and examples of reconstructive uses with this versatile tissue.

Carcinoma

Chemotherapy-related hemolytic-uremic syndrome after the treatment of head and neck cancer. A case report.

A 62-year-old woman who was being treated for squamous cell carcinoma of the head and neck developed a chemotherapy-related hemolytic-uremic syndrome during the second cycle of neoadjuvant chemotherapy consisting of cisplatin, bleomycin, and methotrexate. Though the syndrome was suspected early, attempts at reversing the hematologic and renal abnormalities were unsuccessful. At postmortem examination, the characteristic microvascular lesions of the hemolytic-uremic syndrome were found in the kidneys.

Antineoplastic Combined Chemotherapy Protocols

A randomized study comparing two regimens of neoadjuvant and adjuvant chemotherapy in multimodal therapy for locally advanced head and neck cancer.

Two regimens of neoadjuvant chemotherapy for previously untreated patients with locally advanced head and neck cancer were compared with the goal of identifying a regimen with a greater than 50% complete response (CR) rate. Patients with a performance status of 0 to 2 and normal end-organ function were randomized to receive either four cycles of neoadjuvant methotrexate, cisplatin, and continuous infusion 5-fluorouracil (5-FU) (MPF) (arm A), or four cycles of bleomycin, cisplatin, and methotrexate (PBM) alternating with cisplatin and 5-FU (PF) (arm B). Patients with a performance status of greater than 2 or a carbon monoxide diffusion capacity of less than 50% of the predicted value were assigned to the arm A regimen but were analyzed separately (arm C). Local therapy consisted of surgery (for patients with resectable disease) or radiation therapy followed by two cycles of adjuvant chemotherapy with the regimen that was administered initially. Of the 42 patients who were evaluated, 16 were randomized to arm A, 13 to arm B, and 13 to arm C. The clinical CR rate was 19% on arm A (95% confidence interval, 0% to 38%), 39% on arm B (95% confidence interval, 12% to 66%) (P = 0.41), and 54% on arm C (95% confidence interval, 27% to 81%). At a median follow-up time of 35 months, the 2-year actuarial survival rate was 61% on arm A, 69% on arm B (the P value was not significant), and 38% on arm C. The 2-year survival rate for all 42 patients who were treated was 57% and the median survival time was 31 months. Toxicities of neoadjuvant chemotherapy on all arms consisted of mild to moderate myelosuppression and renal toxicity. The incidence of moderate to severe mucositis was significantly higher on arm A than arm B (P = 0.02). Two cycles of adjuvant chemotherapy were administered to only 11 of 42 patients due to patient refusal or cumulative toxicity. In conclusion, both neoadjuvant chemotherapy regimens resulted in similar response and survival rates, but mucositis was more severe with arm A. However, since neither regimen was likely to cause a CR rate of greater than 50%, this study was closed to further patient accrual.

Adult

Facial reconstruction for radiation-induced skin cancer.

Radiation-induced skin cancers can be difficult to diagnose and treat. Typically, a patient who has received orthovoltage radiotherapy for disorders such as acne, eczema, tinea capitis, skin tuberculosis, and skin cancer can expect that aggressive skin cancers and chronic radiodermatitis may develop subsequently. Cryptic facial cancers can lead to metastases and death. Prophylactic widefield excision of previously irradiated facial skin that has been subject to multiple recurrent skin cancers is suggested as a method of deterring future cutaneous malignancy and metastases. The use of tissue expanders and full-thickness skin grafts offers an expedient and successful method of subsequent reconstruction.

Acne Vulgaris

Radiobiological characterization of head and neck and sarcoma cells derived from patients prior to radiotherapy.

The radiobiological parameters of 33 tumor cell lines were studied in biopsy samples obtained from patients prior to radiotherapy. Epithelial tumor cells derived from head and neck cancer patients were more radioresistant than tumor cell lines derived from patients with sarcoma regardless of method of analysis. The presence of radioresistant tumor cell lines was associated with local failure in some patients. However, the presence of radiosensitive tumor cells did not necessarily predict local control. Our data suggest radiocurability is complex and inherent radiobiological parameters of tumor cells may be only one factor in radiotherapy outcome.

Carcinoma, Squamous Cell

Collagen sheeting implants in cosmetic and reconstructive surgery.

In this study, collagen sheeting is used for correction of various contour deformities of the face. This material, which was used in 16 patients, is easily implanted, does not lead to infection, and has an average resorption rate of 21% at 6 months. It provides excellent cosmetic results.

Adolescent

Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for locally advanced head and neck cancer: a clinical and pharmacologic analysis.

Both cisplatin and leucovorin (LV) interact with fluorouracil (5-FU) by increasing intracellular reduced folate levels and thereby the inhibition of thymidylate synthase. Therefore, the addition of LV to cisplatin and 5-FU (PFL) may increase the activity of that combination in head and neck cancer. We treated 31 patients with locally advanced head and neck cancer with two cycles of neoadjuvant PFL consisting of 100 mg/m2 of cisplatin on day 1 followed by a 5-day continuous infusion of 5-FU at 1,000 mg/m2/day and oral LV at 100 mg administered every 4 hours during the entire duration of chemotherapy infusion. Two patients died during neoadjuvant chemotherapy of sudden death and sepsis, respectively, and were not evaluated for response. Of 29 evaluable patients, nine had a complete response (CR), 17 had a partial response (PR), and three had stable disease. Toxicities consisted of mild to moderate myelosuppression and moderate to severe mucositis, necessitating reduction of 5-FU on cycle 2 to less than or equal to 80% of the intended dose in 22 of 29 patients. Administration of LV by repeated oral dosing resulted in total reduced folate plasma concentrations of 5.3 (+/- 2.9) and 6.7 (+/- 3.4) mumol on days 2 and 4 of the 5-FU infusion. The sum of 1-LV and its metabolite 5-CH3-tetrahydrofolate exceeded the concentration of d-LV, consistent with selective absorption of the biologically active 1-stereoisomer from the gastrointestinal tract.

Adult