Performance and quality of life outcome in patients completing concomitant chemoradiotherapy protocols for head and neck cancer.

This study evaluated post-treatment performance and quality of life (QOL) outcome in head and neck cancer (HNC) patients treated with organ preservation, intensive chemoradiotherapy (FHX). Participants were 47 Stage II-IV HNC patients with no evidence of disease at least one year post-completion of organ preservation, concomitant FHX treatment. Patients were assessed via a semi-structured in-person interview, standardized measures of QOL (FACT-H&N, CES-D), performance (PSS-HN) and patients' perception of residual side effects.

Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor irinotecan in cancer patients.

Purpose: We conducted a pharmacokinetic and pharmacodynamic evaluation of irinotecan (CPT-11) and determined the effect of race and sex on disposition and toxicity of CPT-11. We tested the efficacy of acetaminophen (AAP) to phenotype SN-38 glucuronidation.

Patients And Methods: Forty patients received a dose of 145 mg/m2 of CPT-11 as a 90-minute infusion.

Phase I study of vinorelbine and ifosfamide in advanced non-small-cell lung cancer.

Purpose: We designed a phase I dose-escalation study of vinorelbine on a novel (daily-times-three) schedule with ifosfamide with granulocyte colony-stimulating factor (G-CSF) support to define the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of vinorelbine in this combination.

Patients And Methods: Cohorts of patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) and no prior chemotherapy received vinorelbine starting at 15 mg/m2 on days 1, 2, and 3, and ifosfamide starting at 2.0 g/m2 on days 1, 2, and 3 with G-CSF support for all patients.

Thymidylate synthase expression and response to neoadjuvant chemotherapy in patients with advanced head and neck cancer.

Background: Thymidylate synthase (TS), an essential enzyme in DNA synthesis, is a target for the fluoropyrimidines, an important group of antineoplastic agents used widely in the treatment of head and neck cancer.

Purpose: We evaluated relationships between the level and/or pattern of tumor TS expression and response to fluorouracil (5-FU)-based neoadjuvant chemotherapy in patients with advanced head and neck cancer.

Methods: Tumor specimens from 86 patients were available for this retrospective analysis.

Continuous infusion paclitaxel, 5-fluorouracil, and hydroxyurea with concomitant radiotherapy in patients with advanced or recurrent head and neck cancer.

Concomitant chemotherapy and radiation in the treatment of patients with advanced head and neck cancer is under intense investigation, although the optimal regimen remains undefined. The head and neck cancer program at the University of Chicago has reported encouraging results with concomitant 5-fluorouracil, hydroxyurea, and radiation administered every other week to patients with locally advanced or recurrent disease. The feasibility of adding continuous-infusion paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this combination currently is being tested in a phase I trial.

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.

Long-term response to crisnatol mesylate in patients with glioma.

A total of 26 patients (6 with anaplastic astrocytoma; 20 with glioblastoma) were treated with crisnatol mesylate. All patients had residual or progressive disease following surgery and standard radiotherapy; nine patients had prior chemotherapy. Crisnatol was administered as a 72-hour infusion every 21 days at a starting dose of 2250 mg/m2.

Phase I study of treatment with oral 13-cis-retinoic acid, subcutaneous interferon alfa-2a, cisplatin, and 24-hour infusion 5-fluorouracil/leucovorin.

Unlabelled: A combination of oral 13-cis-retinoic acid (cis-RA) and subcutaneous interferon alfa-2a (IFN) has been reported to yield high response rates in patients with squamous cell carcinomas (SCCAs) of the cervix and skin. Cisplatin and 5-fluorouracil with leucovorin (5-FU/LV) are chemotherapeutic agents commonly used for SCCAs.

Purpose: To determine the maximum tolerated doses (MTDs) of cisplatin and 5-FU/LV when combined with IFN and cis-RA, and to define a recommended phase II regimen for testing in cervical cancer and other appropriate tumor types.

Evaluation of neuropathy in patients on suramin treatment.

Suramin, a promising chemotherapeutic agent, causes a dose-limiting sensorimotor polyneuropathy. We undertook a phase 1 study of suramin that included serial neurologic and electrophysiologic examinations as part of the safety evaluation. We found that 6 of 41 (15%) patients developed suramin-induced demyelinating neuropathy which resembled Guillain-Barre syndrome clinically.

Mineralocorticoid insufficiency due to suramin therapy.

Background: During a Phase I trial of suramin, a novel antineoplastic agent with activity against hormone-refractory prostate carcinoma, the authors observed two patients with clinical mineralocorticoid insufficiency in spite of hydrocortisone replacement therapy.

Methods: The authors retrospectively assessed adrenal cortical function in 20 such patients via adrenocorticotropic stimulation testing, measuring both cortisol and aldosterone responses, either at the time or treatment of immediately after discontinuation of treatment.

Results: Two of 9 patients (22%) treated at relatively low dose levels (< or = 1200 mg/m2 on Day 1) demonstrated adrenal cortical insufficiency, as compared with 9 of 11 patients (32%) treated with relatively high doses (> 1200 mg/m2 on Day 1) (P = 0.

Re-irradiation with concomitant chemotherapy of unresectable recurrent head and neck cancer: a potentially curable disease.

Purpose: The purpose of this study was to review the outcome following concomitant chemoradiation therapy in previously irradiated patients with locally or regionally recurrent or persistent head and neck cancer considered unresectable for cure.

Methods And Materials: We identified 45 patients treated between 1986 and 1993 with unresectable locally or regionally recurrent disease who were treated on one of four concomitant chemoradiotherapy phase I/II studies at the University of Chicago. All patients received hydroxyurea (HU), 5-fluorouracil (5-FU) and concomitant radiation therapy on an alternate week schedule (FHX).

Limited-sampling models for irinotecan pharmacokinetics-pharmacodynamics: prediction of biliary index and intestinal toxicity.

Purpose: To construct limited-sampling models (LSMs) for irinotecan (CPT-11) pharmacokinetic (PK) measures.

Materials And Methods: The recommended phase II dose of weekly CPT-11 administered as a 90-minute infusion is 145 mg/m2 with granulocyte colony-stimulating factor (G-CSF) and maximal antidiarrheal support. Diarrhea is the dose-limiting toxicity.

Ifosfamide-based chemotherapy for non-small cell lung cancer: phase I/II studies at the University of Chicago.

Current clinical investigations in the palliative care setting for patients with non-small cell lung cancer are focused on new drugs and combinations. The goal of these studies is to identify more effective and/or less toxic therapy. At the University of Chicago, we have conducted phase I and II studies to integrate new single agents into novel combination chemotherapy regimens.

Ifosfamide-based combination chemotherapy in advanced non-small cell lung cancer: two phase I studies.

Two studies were performed to determine the maximum tolerated dose (MTD) of paclitaxel and vinorelbine, respectively, in combination with a fixed dose of ifosfamide in previously untreated patients with stage IIIB or IV non-small cell lung cancer. Response rate and survival were also assessed. Both regimens were given with mesna and granulocyte colony-stimulating factor support.

Phase I study of escalating doses of mitoxantrone and paclitaxel with granulocyte-macrophage colony stimulating factor support.

Background: Both paclitaxel and mitoxantrone demonstrate significant antineoplastic activity in breast cancer patients. Colony stimulating factor support allows significant dose escalation of each of these drugs when administered as a single agent.

Methods: We performed a Phase I study employing escalating doses of paclitaxel and mitoxantrone with granulocyte-macrophage colony stimulating factor (GM-CSF) support.

The Performance Status Scale for Head and Neck Cancer Patients and the Functional Assessment of Cancer Therapy-Head and Neck Scale. A study of utility and validity.

Background: The goal of this investigation was to examine the relationship between, and application of, two disease specific quality of life (QL) measures currently being employed for head and neck cancer patients: the Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT-H&N) and the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN).

Methods: The FACT-H&N and PSS-HN were administered to 151 head and neck cancer patients with a range of disease sites, treatment status (on vs. off treatment), and treatment modalities (surgery, radiation, and chemotherapy).

Pharmacodynamics of fluorouracil-based induction chemotherapy in advanced head and neck cancer.

Purpose And Methods: To optimize the biochemical modulation of fluorouracil (5-FU), we administered the pure I-stereoisomer of leucovorin (LV) as a 132-hour continuous intravenous infusion (CIV) with cisplatin 100 mg/m2, 5-FU 640 mg/m2/d as a 120-hour CIV, and interferon alfa-2b (IFN) at 2 MU/m2/d for 6 days for three cycles (I-PFL-IFN). Pharmacologic parameters included morning (AM) and afternoon (PM) plasma concentrations of 5-FU, LV and its active metabolite 5-methyl tetrahydrofolate (MTHF), and dihydropyrimidine dehydrogenase (DPD) activity in peripheral mononuclear cells.

Results: Eighty-nine patients were treated (86 stage IV).

Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival.

Recent studies have shown that p53 mutations are frequently found in cancer of the head and neck, whereas others have indicated that human papilloma virus (HPV) infection may be involved. Thus far, no studies have examined both p53 and HPV in the same patient population and correlated the results with clinical characteristics and outcome. The purpose of this study was to examine any interrelationship between p53 and HPV in patients with squamous cell carcinoma (SCC) of the head and neck.

Vinorelbine (Navelbine), cisplatin, and concomitant radiation therapy for advanced malignancies of the chest: a Phase I study.

Most patients with advanced solid tumors of the chest will have local and/or distant disease progression despite standard therapy. Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) is a new semisynthetic vinca alkaloid with single-agent activity in lung cancer that recently also has been shown to act as a radiosensitizer in vitro. This study aims to define the maximum tolerated dose and dose-limiting toxicity when vinorelbine is given with cisplatin and concomitant radiation therapy.