Biomedical subjects

D J Haraf

Publications and source records attributed to D J Haraf.

68 records · Page 4Linked to original sources

PubMed1992

Neoadjuvant PFL augmented by methotrexate and piritrexim followed by concomitant chemoradiotherapy for advanced head and neck cancer: a feasible and active approach.

To increase the complete remission (CR) rate achieved with two cycles of cisplatin, continuous infusion fluorouracil (5-FU) and oral leucovorin (PFL) we added two antifolate drugs, methotrexate (MTX) and the lipophilic piritrexim (PTX), to the combination (PFL-MP). Twenty-eight patients with previously untreated Stage IV squamous cell carcinoma of the head and neck received 2 cycles of cisplatin 100 mg/m2 on day 1 followed by a 5-day continuous infusion of 5-FU at 800 mg/m2/day and 100 mg of leucovorin administered orally every 4 hours. MTX was administered at 40 mg/m2 IV on day 15 and PTX at 75 mg orally twice daily on days 22 to 26, with cycle 2 starting on day 36. After 2 of the first 5 patients had tumor progression between days 15 and 35, the regimen was intensified to MTX 50 mg/m2, PTX 100 mg twice daily and a cycle duration of 28 days. Local therapy consisted of surgery and/or radiotherapy with concomitant 5-FU and hydroxyurea (FHX) administered every other week. Eleven patients (39%, 95% confidence intervals 21-57%) had a CR, 9 (32%) had a PR, and four patients had no response. Four patients were unevaluable for response to PFL-MP. Patients with poor performance status or N3 disease were less likely to achieve a CR. Mucositis following PFL was the dose-limiting toxicity. Local therapy included surgery in 15 patients and FHX chemoradiotherapy in 19 patients. The administration of FHX in this setting proved feasible and the regimen was given near the intended dose intensity in the majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

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↗

PubMed1992

The evolving role of systemic therapy in carcinoma of the lung.

Locally advanced lung cancer carries a poor prognosis, and its treatment continues to challenge medical, radiation, and surgical oncologists. While systemic chemotherapy has improved the survival of patients with small cell lung cancer (SCLC), the role and timing of thoracic radiotherapy has not been clearly defined. The roles of chemotherapy and radiotherapy appear to be reversed in the treatment of locally advanced non-small cell lung cancer (NSCLC). The routine use of thoracic radiotherapy has been shown to improve local control after surgery without affecting survival, due to a high incidence of distant metastases. This contrasts with the marginal survival benefit seen with chemotherapy in NSCLC. Nevertheless, the results of recent clinical trials in both SCLC and NSCLC are encouraging and support continued investigation. These studies and the results of recent pilot studies suggest that a closer integration of chemotherapy and radiotherapy (concomitant chemoradiotherapy) may be necessary for further improvement in outcome. This review will present the results of recent studies in systemic therapy of lung cancer and the evidence supporting concomitant chemoradiotherapeutic treatment of this disease.

Carcinoma, Non-Small-Cell Lung↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1991

Measurement of bioreduction rates of cells with distinct responses to ionizing radiation and cisplatin.

A low frequency electron paramagnetic resonance (EPR) spectrometer has been used to measure the bioreduction rate of an exogenously added nitroxide free radical species. Measurements have been made in a well controlled, in vitro system using an X-ray and cisplatin sensitive Chinese hamster ovary (CHO) cell line, xrs-5, and partial revertants which display wild-type levels of sensitivity to X-rays but retain xrs-5 levels of cisplatin sensitivity. The xrs-5 cells reduce this radical species at a rate which is approx. 50% that of the wild-type CHO cell line, K1. The partial revertants maintain this defect in bioreduction despite their decrease in radiosensitivity. However, the bioreduction rate observed in these cells correlates with their sensitivity to the chemotherapeutic drug cisplatin. Low frequency EPR allows measurements and imaging of living tissue and may be of value as a predictive assay of human tumor response to chemotherapy.

Animals↗

PubMed1991

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↗

PubMed1991

Radioresistant derivatives of radiosensitive CHO cells obtained following treatment with 5-azacytidine retain their sensitivity to cisplatin.

Treatment of the radiation-sensitive CHO mutant, xrs-5, with the demethylating agent 5-azacytidine results in the complete conversion to wild-type levels of X-ray resistance in 50% of the colonies examined (10/20). In addition to being sensitive to X rays, xrs-5 is also sensitive to the killing effects of the crosslinking agent cisplatin. The 5-azacytidine-treated xrs-5 cells which exhibit wild-type survival levels following exposure to X rays failed to demonstrate conversion to wild-type levels of resistance to cisplatin. These results support the hypothesis that increases in gene expression can alter the radioresistance of xrs-5 cells without influencing the cells' survival after exposure to cisplatin.

Animals↗

PubMed1990

Radiation therapy in the treatment of cervical cancer: the University of Chicago/Michael Reese Hospital experience.

A retrospective analysis was conducted on 307 patients referred for radiation therapy at The University of Chicago and Michael Reese Hospital between 1971 and 1986. Median follow-up was 6.4 years. Treatment techniques varied during the time of the study. Actuarial disease-free survivals were 78%, 64%, 55%, 33%, 41%, and 60% for stage IB, IIA, IIB, IIIA, IIIB, and IVA, respectively. Stage, size of the cervical lesion, and hemoglobin level during treatment were prognostic factors. Treatment technique as well as time dose factors were analyzed with respect to survival, failures, and complications.

Adult↗

PubMed1989

Beam's-eye-view aided treatment planning for a nasopharyngeal lesion: a case report.

We report on the application of CT-based multilevel treatment planning to achieve complete and uniform dose distribution over the entire target while sparing critical structures. Treatment strategy and parameters are chosen on the slice containing the isocenter. Target coverage and organ sparing is achieved on all other slices by independently adjusting the asymmetric field width at each level, stimulating the effects of custom blocks. The optimized field borders are back projected using beam's eye views (BEV) from each treatment angle. The BEV printouts are used to assist the physician in the delineation of field blocking on the simulation films.

Humans↗

PubMed1988

Treatment selection in T1 and T2 vocal cord carcinoma.

Radiation therapy is the treatment of choice for most patients with T1 and T2 carcinomas of the vocal cord, resulting in high rates of local control and preservation of voice. Though surgical options also result in high rates of local control, vocal quality is inferior. Endoscopic laser surgery has been used only on small numbers of selected T1 lesions. Its role needs to be defined as vocal quality tends to be inferior to radiation therapy and substantial numbers of patients require additional treatment.

Combined Modality Therapy↗

PubMedDate not supplied

Osteoradionecrosis of the jaws as a risk factor in radiotherapy: a report of an eight-year retrospective review.

Osteoradionecrosis of the jaws is a severe complication of radiotherapy in the treatment of the head and neck neoplasms. The literature indicates a recent decline in the reported incidence of this complication. The purpose of this study was to further assess the incidence rate for osteoradionecrosis. Factors previously associated with an increased risk for osteoradionecrosis were evaluated to determine possible relationships. A retrospective chart review was conducted for 193 patients treated with radiotherapy for malignant head and neck tumors over an eight-year period. Recorded diagnoses of osteoradionecrosis were noted. Factors previously correlated with the development of osteoradionecrosis were assessed. Of the 193 charts reviewed, 9 diagnoses of osteoradionecrosis of the jaws were made representing an incidence rate of 4.7% for the period evaluated. No single factor was noted to be associated with the development of osteoradionecrosis. The results indicate a low incidence rate for osteoradionecrosis as a post-radiation treatment complication. No single causative factor could be identified suggesting a multifactorial interaction responsible for osteoradionecrosis.

Aged↗

PubMedDate not supplied

Multimodality therapy in advanced paranasal sinus carcinoma: superior long-term results.

PURPOSE: This study was conducted to determine the efficacy of multimodality treatment for stage III and IV, locoregionally advanced paranasal sinus carcinoma. PATIENTS AND METHODS: A subgroup analysis of 19 consecutive patients with stage III or IV paranasal sinus carcinoma treated with multimodality therapy from head and neck cancer protocols between 1984 and 1996 were analyzed for outcome. Sixteen patients received induction chemotherapy consisting of three cycles of cisplatin and 5-fluorouracil, followed by traditional resection (14 patients) or surgical debulking (two patients). Surgery was followed by concomitant chemoradiotherapy with hydroxyurea and 5-fluorouracil in a week-on, week-off sequence in 15 patients. One patient received standard radiation therapy. An additional three patients were treated with a sequence of surgical resection followed by concomitant chemoradiotherapy. The median total dose to the primary tumor was 60 Gy (range, 45-74 Gy). RESULTS: The overall survival at 5 and 10 years by lifetable analysis was 72.7% and 53.9%, respectively, and the disease-free survival at both 5 and 10 years was 66.6%. Local control was 76.1% at both 5 and 10 years. In the subgroup of patients treated with induction chemotherapy, 87% (14/16) achieved a clinical response. A complete response was confirmed at the time of surgery in five patients, whereas 11 patients had residual disease in the surgical specimen. Regional and distant failures were unusual (one patient each), with a 10-year regional control rate of 93% and a distant control rate of 95.5%. Serious, nonreversible long-term complications included two cases of unilateral blindness, one cataract, and one case of ototoxicity. DISCUSSION: An excellent long-term outcome with respect to local control, overall survival, and disease-free survival is achieved in locoregionally advanced paranasal sinus cancer treated with induction chemotherapy, surgery, and concomitant chemoradiotherapy. The 15 patients treated with this regimen had 10-year overall survival, disease-free survival, and local control rates of 56%, 73%, and 79%, respectively. These results are encouraging and are superior to the 40% survival achieved with surgery and radiation therapy. Further investigation of this regimen is warranted.

Adult↗

PubMedDate not supplied

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

PURPOSE: Locoregionally advanced oropharyngeal 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. Herein, we report overall survival, progression-free survival, and patterns of failure in locoregionally advanced oropharyngeal cancer treated with induction chemotherapy with or without conservative surgery followed by concomitant chemoradiation. MATERIALS AND METHODS: Three cycles of induction chemotherapy consisting of cisplatin, 5-fluorouracil, leucovorin, and interferon alpha-2b (PFL-IFN) were followed by conservative, organ-sparing surgery for residual disease. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-fluorouracil, hydroxyurea, and a total radiotherapy dose of roughly 7,000 cGy. RESULTS: Sixty-one patients with predominantly stage IV disease were treated. Clinical complete response was observed in 65% of patients after induction therapy. The median follow-up was 68.0 months for survivors and 39.0 months for all patients. At 5 years, overall survival is 51%, progression-free survival is 64%, locoregional control is 70%, and distant control is 89%. Locoregional recurrence accounted for 80% of all initial failures. Only five radical surgeries (none were total glossectomy) were performed for initial disease control. Treatment-related toxicity accounted for four deaths. CONCLUSION: PFL-IFN given with 5-fluorouracil, hydroxyurea, and radiotherapy produces a high rate of cures with organ preservation in a disease group that has traditionally fared poorly. Local and distant disease control and survival rates exceed those observed with more standard treatment approaches involving surgery and radiotherapy. Further investigation into chemoradiotherapy as a curative modality for this disease is warranted.

Adult↗