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Biomedical subjects

P Dady

Publications and source records attributed to P Dady.

8 recordsLinked to original sources
PubMed1999

Causes for increased myelosuppression with increasing age in patients with oesophageal cancer treated by chemoradiotherapy.

The aim of this study was to identify why increasing myelosuppression accompanies increasing age in patients treated for oesophageal cancer by chemoradiation. Weekly neutrophil and platelet counts were obtained throughout treatment in 86 patients undergoing chemoradiation without surgery for oesophageal cancer. One or two cycles of cisplatin 80 mg/m2/day followed by 5-fluorouracil 800 mg/m2/day for 4-5 days were administered during the first and fourth or fifth week of radiotherapy using 2 Gy daily fractions. 44 of the patients underwent 5-fluorouracil pharmacokinetic studies. Multiple regression procedures were used to determine the strength of factors that contribute to initial and nadir neutrophil and platelet counts. The kinetics of myeloid response were evaluated from the rates of disappearance and re-appearance of neutrophils and platelets during treatment. Age, fluorouracil dose (or AUC), baseline body weight and neutrophil (or platelet) count were found to be powerfully and independently predictive of both first neutrophil and platelet nadir count. Baseline neutrophil and platelet counts were also found to correlate negatively with advancing age independently of other factors. The rate of descent of both indices, however, was independent of age, baseline count and fluorouracil dose suggesting that variations in the size of the myeloproliferative compartment prior to treatment were responsible for interpatient variations. In addition, the rate of recovery of both indices was not influenced by age amongst patients in whom data was assessable suggesting that proliferation of surviving marrow elements is not compromised by age. These data are compatible with the hypothesis that a progressive depletion of the myeloid stem cell compartment accompanies advancing age, and that this is responsible for increasing myelotoxicity.

Adult↗
PubMed1999

Simultaneous adjuvant radiotherapy and chemotherapy for stage I and II breast cancer.

The purpose of the present paper was to evaluate treatment outcome after conservative breast surgery or mastectomy followed by simultaneous adjuvant radiotherapy and cyclophosphamide, methotrexate and fluorouracil (CMF) therapy. Two hundred and sixty eight (268) patients were treated at two Australian and two New Zealand centres between 1981 and July 1995. One hundred and sixty-nine patients underwent conservation surgery and 99 had mastectomies. Median follow-up was 53 months. Conventionally fractionated radiation was delivered simultaneously during the first two cycles of CMF, avoiding radiation on the Fridays that the intravenous components of CMF were delivered. In conservatively treated patients, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 34.5 +/- 5.2%, 25.4 +/- 4.5% and 75.5 +/- 4.8%, respectively. Crude incidence of local relapse at 4 years was 6.3% and at regional/distant sites was 26.3%. Highest grades of granulocyte toxicity (< 0.5 x 10(9)/L), moist desquamation, radiation pneumonitis and persistent breast oedema were recorded in 10.7, 8.5, 8.9 and 17.2%, respectively. In patients treated by mastectomy, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 59.7 +/- 7.3%, 56.7 +/- 7.4% and 50.1 +/- 7%. The crude incidence of local relapse at 4 years was 5.6% and at regional/distant sites it was 45.7%. The issue of appropriate timing of adjuvant therapies has become particularly important with the increasing acknowledgement of the value of anthracycline-based regimens. For women in lower risk categories (e.g. 1-3 nodes positive or node negative), CMF may offer a potentially better therapy, particularly where breast-conserving surgical techniques have been used. In such cases CMF allows the simultaneous delivery of radiotherapy with the result of optimum local control, without compromise or regional or systemic relapse rates. Further randomized trials that directly address the optimal integration of the two modalities, such as the one carried out in Boston, are clearly necessary.

Adult↗
PubMed1998

Pharmac--what next?

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Clinical Trials as Topic↗
PubMed1995

Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer--toxicity and dose modification: a Transtasman Radiation Oncology Group Multi-Institution study.

PURPOSE: To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities. METHODS AND MATERIALS: One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone. RESULTS: Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect. CONCLUSION: Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification.

Adult↗
PubMed1992

A clinical and pharmacological study of high-dose mitozolomide given in conjunction with autologous bone marrow rescue.

In conjunction with autologous bone marrow rescue, high-dose mitozolomide was given i.v. to 16 patients with refractory malignancies at doses ranging from 100 to 400 mg/m2 over 1 h. Neutropaenia occurred consistently at 300 mg/m2, and three trivial infective episodes were recorded. Thrombocytopaenia occurred consistently at 150 mg/m2, and three patients experienced episodes of minor bleeding. The death of one subject was attributable to pulmonary thromboembolism during the bone marrow reinfusion. Transient emesis and mild alopecia were the only other toxicities. Three of six evaluable patients receiving greater than or equal to 300 mg/m2 exhibited measurable reductions in tumour dimensions, although these failed to fulfil the criteria for a partial response. Mitozolomide was undetectable in plasma at 12 h after drug administration. The plasma pharmacokinetic data fitted mono- or biexponential models in all patients. Model-independent pharmacokinetic parameters were: peak plasma drug concentration, 3.4-46 mg/l; AUC, 8-82 mg h l-1; clearance, 7.6-45 l/h; steady-state volume of distribution, 11-85 l; and plasma elimination half-life, 1.4-2.8 h. Dose-dependent pharmacokinetics were not observed, and only a small percentage of the delivered dose was eliminated unchanged in the urine. The maximally tolerated dose of mitozolomide given with autologous bone marrow rescue was greater than 400 mg/m2. At this dose myelosuppression was the only major toxicity, and the plasma drug levels and AUC values were comparable to those obtained after therapeutic doses in experimental models.

Adult↗
PubMed1986

Cisplatin neuropathy with Lhermitte's sign.

Following chemotherapy with cis-diamminedichloroplatinum II (cisplatin) three patients developed Lhermitte's sign and peripheral neuropathy. The toxic side effects did not become apparent until after treatment had ceased. Because of increasing use of cisplatin to achieve lasting remission in patients with malignant disease proprioceptive and myelopathic side effects may become increasingly common.

Adult↗
PubMed1983

Assessment of response of bone metastases to systemic treatment in patients with breast cancer.

Seventy-one patients with breast cancer and bone metastases, together with other assessable sites of disease, were monitored by radiologic skeletal survey, bone scanning, pain charts, bone marrow aspirate, serum calcium, alkaline phosphatase and urine hydroxyproline/creatinine ratio. On the basis of UICC criteria of response in nonosseous sites, 37 were classed as responders and 34 as nonresponders. Responding patients with osteolytic disease frequently showed sclerosis, but only at 6-8 months, whereas patients with mixed lytic/sclerotic or sclerotic metastases frequently showed no change or further sclerosis. Nonresponders most frequently showed progressive lysis. Bone scanning showed clear evidence of improvement or deterioration in 7/21 responders and 8/23 nonresponders who showed no definite evidence of progression or response on skeletal radiography. Pain assessment was also useful in these patients. Neither the bone marrow aspirate nor other biochemical tests were useful in assessing response to therapy. This study concludes that bone scanning and pain assessment are both useful in assessment of response of bone metastases to treatment in some patients and incorporation into a standard criteria of response is recommended.

Alkaline Phosphatase↗