Julie A. Kish

Cisplatin and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck.

The combination of cisplatin and 96‐hour infusion of 5‐fluorouracil (5‐FU) was evaluated in 30 patients with recurrent (local and regional) and disseminated histologically proven epidermoid cancer of the head and neck who failed surgery and radiotherapy. Cisplatin 100 mg/M2 intravenous (IV) bolus was given on day 1 with hydration and mannitol diuresis; 5‐FU 1000 mg/M2 per day for 96‐hour infusion was started immediately after cisplatin on day 1. All patients had measurable lesions. Eight (27%) patients achieved complete response (CR), and 13 (43%) had partial response (PR). Overall response rate was 70% (8 of 30 CR and 13 of 30 PR). Response rate in patients with recurrent local and regional disease was 89% (17/19) with median survival of 32 weeks, while response in patients with disseminated disease was 36% (4/11) with median survival of 24 weeks. Patients with good performance status (PS) (<70%) had a response rate of 79% (19/24), while those with poor PS (<70%) had a response rate of 33% (2/6). Seven patients with recurrent disease who had a response to this chemotherapy went to further salvage surgical procedures. It is concluded that the combination of cisplatin and 5‐FU is very effective and well tolerated in these patients, and leads to further salvage in some patients with improved longevity and quality of life.

A randomized trial of cisplatin (CACP) + 5-fluorouracil (5-FU) infusion and CACP + 5-FU bolus for recurrent and advanced squamous cell carcinoma of the head and neck

One of the most active chemotherapeutic regimens for treatment of advanced and recurrent head and neck cancer is cisplatin (CACP) + 5‐fluorouracil (5‐FU) infusion with a response rate of 90% in advanced, previously untreated patients and 70% in patients with recurrent disease. Forty‐four patients from two Wayne State University‐affiliated hospitals were entered into a randomized trial of CACP (100 mg/m2) day 1 and 24‐hour infusion of 5‐FU (1000 mg/m2) days 1 through 4 versus CACP (100 mg/m2) day 1 and bolus 5‐FU (600 mg/m2) day 1 and day 8. Thirty‐eight patients were evaluable for three induction courses. Response for the infusion arm was 72% (4/18 complete response [CR] + 9/18 partial response [PR]). Response for the bolus arm was 20% (2/20 CR + 2/20 PR). The difference in response was statistically significant by chi‐square analysis (P < 0.01). Seventy percent of the patients on the bolus arm experienced leukopenia with several episodes of grades 3 and 4 leukopenia. In addition, 50% of the patients on the bolus arm experienced thrombocytopenia. Stomatitis was more frequent on the infusion arm but it was mild and reversible. The complete responders on either arm have a median survival of 120+ weeks; partial responders, 30 weeks. Cisplatin + 5‐FU infusion produces a superior response as initial chemotherapy for three courses compared with CACP and 5‐FU bolus.

Cis-platinum and 5-fluorouracil as induction therapy for advanced head and neck cancer

Sixty-one patients were treated with a three course induction regimen of 5-fluorouracil and cis-platinum for advanced squamous cell carcinoma of the head and neck area. Thirty-three patients (54 percent) had complete clinical remission with the administration of these drugs. Twenty-four patients (39 percent) showed a 50 percent or greater reduction in tumor size, for a significant response rate of 93 percent. The toxicities were within acceptable limits, and only three patients did not complete all three courses. Surgery and radiation therapy were supposed to follow the chemotherapy but several patients refused surgery after the disappearance of their lesion. This has created a problem in patient management.

Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer.

In a series of three consecutive pilot studies conducted between 1977 and 1982 at Wayne State University, Detroit, Michigan, 191 consecutive patients with previously untreated, locally advanced head and neck cancer were treated with cisplatin (CDDP), vincristine, and bleomycin or CDDP and 5‐fluorouracil (5‐FU) infusion before definite surgery or radiation. A 39% (75/191) rate of complete clinical responses was achieved. Thirty‐two of the chemotherapy‐induced complete responders underwent radical surgery. Thirteen had no histologic evidence of residual disease in the surgically resected specimen. The CDDP and 5‐FU infusion combination achieved the highest histologic complete response rate. All histologically complete responders who had completed local radiation therapy are clinically free of disease at median follow‐up of 36 months. Patients who achieved complete response both clinically and histologically had superior survival as compared to patients who achieved complete response clinically and were subsequently found to have residual tumor in their surgically resected specimen (P = 0.01). An analysis of the clinical and pathological pretreatment characteristics was performed to identify factors predictive of histologic complete response. Advanced nodal disease correlated inversely with the achievement of negative histology in the surgically resected specimen (P = 0.02). No other factors were significant in predicting response. Cancer 59:233–238, 1987.

Metastatic squamous cell carcinoma of an unknown primary localized to the neck. Advantages of an aggressive treatment

Treatment of patients with squamous cell carcinoma (SCC) of an unknown primary localized to the neck is still controversial, particularly regarding advanced disease. We reviewed 41 such patients treated with surgery and/or radiotherapy (RT) (n = 25) or with combined modality treatment including chemotherapy (CH) (n = 16). The male to female ratio was 28 to 13, and the median age was 58 years (range, 32 to 94 years). There were 27 (66%) patients with poorly differentiated SCC and 8 with moderately differentiated or well‐differentiated cancer. Twenty‐three (56%) patients had N3 disease, 16 (39%) had N2, and 2 had N1. The majority of N3 patients have been treated with CH and RT (n = 12) or with RT alone (n = 9). The combined CH‐RT was well tolerated, with no life‐threatening toxicity. The complete response (CR) to CH‐RT was 81% (11 patients have no evidence of disease [NED] currently). The median survival time of this group was 37+ months. Of the 25 patients who had surgery and/or RT as their first planned treatment, 7 (28%) have NED currently. The median survival time of this group was 24 months. Patients with N3 disease who received CH had a higher CR rate and a longer survival time as compared with those treated with surgery and/or RT, despite a higher (N3) stage of disease. These findings warrant further investigation in randomized cooperative studies.

The Incidence and significance of thromboembolic complications in patients with high-grade gliomas

Coagulation system abnormalities in patients with malignancy ranges from asymptomatic laboratory abnormalities to overt clinical manifestations. To determine the incidence and significance of clinically manifest thromboembolic phenomena in patients with high‐grade gliomas, the records were analyzed of 77 patients that presented between January 1985 and June 1988. Fifteen patients (19%) had clinically manifest deep venous thrombosis and/or pulmonary emboli during the course of their disease. All these patients were ambulatory before and at the time of diagnosis of the event. The thromboembolic episodes occurred at the time of initial management of the primary tumor while there was documented clinical improvement in the functional status of the patient or at the time of progression of the disease. One patient died as a result of a pulmonary embolism; in two others, an embolism was a significant contributor to the patients death. Anticoagulation resulted in complications in two of eight patients treated. Thromboembolic events occur with high frequency in patients with high‐grade gliomas and contribute to the high morbidity and mortality seen in these patients. The optimum approach to screening and the treatment of these events has not been determined. Cancer 68:2621–2624, 1991.

5-Fluorouracil Cardiotoxicity: Left Ventricular Dysfunction and Effect of Coronary Vasodilators

ABSTRACT: Seven patients developed clinical features simulating myocardial ischemia less than 72 hours after 12 of 13 separate invenous 5-flourouracil administrations; 9 episodes were associated with chest pain, 3 with hypotension, 3 with ventricular tachycardia and 1 with cardiogenic shock. Left ventricular dysfunction was demonstrated by echocardiography in 5 separate episodes, 2 with interval improvement upon repeat echocardiograms. Pretreatment with nitrates and/or calcium channel blockers failed to prevent recurrence of cardiotoxicity during 5 of 6 repeat 5-fluorouracil administrations. Therapy with 5-fluorouracil is associated with cardiotoxicity simulating myocardial ischemia with left ventricular dysfunction. Pretreatment with coronary vasodilators may not prevent this phenomenon.

Excellent response to cis-platinum-based chemotherapy in patients with recurrent or previously untreated advanced nasopharyngeal carcinoma

Twenty-four patients with recurrent and/or locally advanced nasopharyngeal carcinoma who received cis-platinum-based chemotherapy are reported. Twelve patients with recurrent disease previously treated with radiotherapy received cis-platinum-based chemotherapy. An overall response rate of 67% (8/12) and a complete response (CR) of 25% (3/12) were achieved. All the CR patients were treated with cis-platinum and 5-fluorouracil (5-FU) infusion. Twelve patients with locally advanced (stage IV) previously untreated nasopharyngeal carcinoma received cis-platinum-based chemotherapy. Eight of those patients received cis-platinum and 5-FU combination chemotherapy followed by radiation therapy. An overall response of 75% (6/8) and a complete response of 50% (4/8) were achieved by induction chemotherapy. Subsequent radiation therapy to the 6 responding patients (CR 4, PR 2) to chemotherapy increased the complete response to 100% (6/6). The other two stable patients refused further therapy and died in less than 1 year from locoregional disease. Four patients were treated with concurrent cis-platinum and radiation therapy. A complete response of 100% (4/4) was achieved.

The role of infection in the morbidity and mortality of patients with head and neck cancer undergoing multimodality therapy

Cancer of the head and neck is a common cancer worldwide. The majority of patients present with locally advanced disease. Recently a great deal of improvement has been made in multimodality therapy of this disease, warranting more careful consideration of factors affecting quality of life, disease course, and treatment. Infection is clearly a factor. Analysis of 662 hospital admissions of 169 head and neck cancer patients was performed. A definite infection was documented in 86 febrile episodes, pneumonia contributed to 40%, bacteremia to 13%, skin and soft tissue infection to 12%, and tracheobronchitis to 10%. Among the evaluated risk factors, foreign bodies, specifically intravenous (IV) cannulae and gastrostomy tubes, race, performance status, alcohol intake, and nutritional status were statistically significant variables that predicted for or were associated with infection. Infection contributed to 44% of the deaths.

Chemotherapy for paranasal sinus carcinoma: a 10-year experience at Wayne State University

The role of chemotherapy in the management of patients with cancer of the paranasal sinus has not been defined. An analysis of 24 evaluable patients treated with chemotherapy as part of their overall therapy was performed. There were 16 male patients and eight female patients. Sixteen patients were previously untreated and eight had recurrent disease after surgery and/or radiotherapy. Six of the previously untreated patients had metastatic disease on presentation (four central nervous system (CNS) and two lung), and four recurrent patients had CNS involvement. The majority of patients (78%) had squamous cell carcinoma. The chemotherapy regimens included cisplatin (CDDP), vincristine (VCR), and bleomycin (COB), 5‐fluorouracil (5‐FU) infusion and CDDP, or 5‐FU/CDDP and methotrexate (MTX). All patients had computed tomography (CT) measurable disease. Previously untreated patients underwent surgery and/or radiotherapy postchemotherapy. The overall response rate to chemotherapy for previously untreated patients was 82% (complete response [CR] 44%, partial response [PR] 38%) and for recurrent patients 88% (CR 38%, PR 50%). Predominant toxicities were nausea, vomiting, myelosup pression, mucositis, and renal impairment. The median survival of the previously untreated patients, based on response to chemotherapy, was as follows: CR 21+ months (range, 10+ to 81 months), PR 13.5 months (range, 2 to 21 months), and no response (NR) 3 months (range, 1 to 7 months). The median survival of patients with recurrent disease was as follows: CR 16 months, PR 13.5 months, and NR 5 months. We conclude that patients with paranasal cancers are responsive to CDDP‐containing combinations. The role of adjuvant chemotherapy in previously untreated, locally advanced patients needs to be demonstrated by future randomized trials.