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P Kirkbride

Publications and source records attributed to P Kirkbride.

34 records · Page 2Linked to original sources
PubMed1997

A phase I/II study of paclitaxel (TAXOL) and concurrent radiotherapy in advanced nonsmall cell lung cancer.

PURPOSE: The addition of chemotherapy to radical radiotherapy (XRT) has been shown to improve survival in locally advanced nonsmall cell lung cancer (9). Consequently, different chemotherapeutic regimens in combination with XRT are being evaluated in the treatment of this disease. Paclitaxel (TAXOL) may be a valuable drug in this situation as, in addition to a demonstrated activity in NSCLC, it has been shown to enhance the effect of radiation on cell lines in vitro. METHODS AND MATERIALS: Seventeen patients were enrolled onto a Phase I/II trial to determine the maximum tolerated dose of paclitaxel given by a 3-h infusion every 2 weeks throughout a 6-week course of XRT, 60 Gy in 30 daily fractions, in patients with Stage III NSCLC and then to describe the response rate of this combination in an expanded cohort of patients treated at the recommended phase II dose. Three patients were entered at each dose level (45, 90, 120, and 135 mg/m2), except for the 120 mg/m2 dose level, which was expanded to nine patients. RESULTS: The dose limiting toxicity was neutropenia--two of three patients treated at the 135 mg/m2 level experienced Grade 3 neutropenia on day 15, which precluded administration of scheduled chemotherapy. Esophagitis was mild to moderate, and although profound lymphopenia was observed at all dose levels, there was no evidence of associated opportunistic infections. Of the nine patients treated at the recommended Phase II dose of 120 mg/m2, there were one complete and six partial responses (response rate 78%). CONCLUSION: The combination of XRT, 60 Gy in 6 weeks and paclitaxel, 120 mg/m2 q 2 weeks, can be safely given to patients with NSCLC, and although it demonstrates activity in this situation, consideration should be given to the addition of other agents, such as platinum compounds.

Antineoplastic Agents, Phytogenic↗
PubMed1996

The role of palliative radiotherapy for bone metastases.

Painful bone metastases are a clear indication for the use of radiotherapy, with reported response rates of up to 85% of patients treated. In an attempt to define the optimal use of palliative radiotherapy when used in this situation, the data for the efficacy, toxicity and choice of dose and fractionation are reviewed. Although there have been some recent trials demonstrating the value of hypofractionated radiation therapy, half-body irradiation and 89-strontium, in general there is a lack of information in this clinical area, particularly on the duration of beneficial effect and on treatment toxicity. The available data suggest that single-fraction radiation is as effective as short-course fractionated treatment, and may be isotoxic when 5HT3 antagonists are used. Future implications for research are discussed.

Bone Neoplasms↗
PubMed1996

How should we design trials of palliative radiotherapy?

Some of the issues to be considered when designing trials of palliative treatments, and specifically palliative radiation therapy, are discussed. In particular the concepts of entry criteria, endpoints, measurement of response variables and follow-up, and how they might be applied in these situations are considered.

Clinical Trials as Topic↗
PubMed1995

Proliferation measurements with flow cytometry Tpot in cancer of the uterine cervix: correlation between two laboratories and preliminary clinical results.

PURPOSE: To assess the prognostic value of the pretreatment potential doubling time (Tpot) in carcinoma of the uterine cervix, relative to other established clinical factors. METHODS AND MATERIALS: Fifty-two patients with cervical cancer were studied prospectively from March 1991 to October 1993. Pretreatment evaluation included examination under anesthesia and tumor biopsy 6 h following the intravenous administration of bromodeoxyuridine (200 mg). Tpot was determined by deriving the labeling index (LI) and S-phase synthesis time (Ts) using flow cytometry. Six patients were not evaluable and excluded. The remaining 46 patients (average age 55 years) were treated uniformly with radical radiation therapy. There were 39 squamous carcinomas and 7 adenocarcinomas. Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stages were: Ib and IIa, 12 patients; IIb, 18 patients; III and IV, 16 patients. The median external beam dose was 50 Gy (range, 45-52.8 Gy) delivered in 25 fractions. The median intracavitary dose was 40 Gy (range. 25.5-40 Gy) delivered with a single line source to a point 2 cm lateral of the midline, with a mean dose rate of 0.71 Gy/h. The median overall treatment time was 45 days (range, 34-73 days). As of July 31, 1994, 12 patients had died of disease, and the average follow-up for alive patients was 1.4 years (range, 0.5-3.3 years). RESULTS: There were 27 tumors with diploid deoxyribonucleic acid (DNA) content and 19 tumors were aneuploid. The median and mean Tpot for the 46 patients were 5.5 and 6.6 days, respectively [range, 2.0-25.6 days; coefficient of variation (CV), 74%]. For 25 patients where Tpot measurements were performed at two separate laboratories, there was a fair correlation (r = 0.74), but systematic differences were detected suggesting that the lack of agreement was not simply due to intratumoral variation. To date, 30 patients remained disease free, while 8 patients had pelvic failure and 9 patients developed distant metastases as the first failure site (1 patient developed both at the same time). In univariate analysis, the only significant prognostic factor for disease-free survival was tumor size (p = 0.004). A short Tpot (or high LI) and long overall treatment time (OTT) were weakly associated with poorer disease-free survival, although not statistically significant (1/Tpot, p = 0.14; LI, p = 0.23; OTT, p = 0.04). Age, FIGO stage, hemoglobin level, S-phase fraction, DNA ploidy, and Ts were not associated with disease-free survival. Multiple regression analysis was not performed because of the relatively small number of patients and short follow-up. CONCLUSIONS: Tpot values determined with current techniques by different laboratories cannot be used interchangeably for the purpose of therapy decisions. Vigorous quality assurance and standardization of the laboratory procedures and analysis methods are important to reduce interlaboratory variation. In this uniformly treated group of patients with cancer of the uterine cervix, traditional clinical prognostic factors remain the most important. Preliminary data suggest that the flow cytometry-determined Tpot and labeling index predict for disease-free survival, although a larger number of patients with longer follow-up is required to assess the true prognostic significance of these assays and to determine if their effect is independent of other clinical factors.

Adenocarcinoma↗
PubMed1995

Carcinoma of the vagina--experience at the Princess Margaret Hospital (1974-1989).

The charts of 153 patients with vaginal carcinoma or carcinoma in situ seen at Princess Margaret Hospital between 1974 and 1989 were analyzed with respect to treatment modality, radiation dose and technique, complications, and survival. One hundred and twenty-eight patients were treated with radiation therapy, of which 10 received radiation postoperatively and 26 concomitant chemotherapy. The overall 5-year actuarial cause-specific survival was 66%. The 5-year cause-specific survivals by stage were Stage 0 (C-I-S) 100%, Stages I/II 77%, and Stages III/IV 56%. Late complications from treatment were infrequent and in only 12 patients were such complications classified as severe. Univariate analysis indicated that size and stage of tumor, histological grade, patient age, and radiation dose > 7000 cGy were significant factors in predicting survival, although in a multivariate analysis only size and stage retained significance. Fifty-one patients had a prior gynecological malignancy arising 1-37 years previously, of which 34 had cervical cancers. Radiotherapy is an effective treatment for all stages of carcinoma of the vagina and doses of at least 7000 cGy are recommended to maximize tumor control.

Actuarial Analysis↗
PubMed1995

Prognostic factors in patients with cervix cancer treated by radiation therapy: results of a multiple regression analysis.

A retrospective analysis of 965 patients with invasive cervix cancer treated by radiation therapy between 1976 and 1981 was performed in order to evaluate prognostic factors for disease-free survival (DFS) and pelvic control. FIGO stage was the most powerful prognostic factor followed by radiation dose and treatment duration (P values = 0.0001). If the analysis was limited to patients treated with radical doses of 75 Gy or more, dose was no longer significant. Young age at diagnosis, non-squamous histology and transfusion during treatment were also adverse prognostic factors for survival and control. Para-aortic nodal involvement on lymphogram was associated with a reduction in DFS (P = 0.0027), whereas pelvic lymph node involvement alone was not. In patients with Stage I and IIA disease, tumour size was the most powerful prognostic factor for survival (P = 0.0001) and the extent of pelvic sidewall involvement was significant in patients with Stage III tumours (P = 0.007). Histological grade appeared to be a predictive factor but was only recorded in 712 patients. These features should be considered in the staging of patients and in the design of clinical trials.

Adult↗
PubMed1995

The role of radiation therapy in palliative care.

Radiation therapy plays a significant role in the palliation of symptoms of patients with malignant disease. This article looks at the scientific and clinical rationales for its use and discusses some of the current controversies in palliative radiotherapy. The utility of radiation therapy is discussed and potential side effects are described. Radiation oncologists are important members of the multidisciplinary team providing palliative care. Their involvement in the care of patients with advanced or metastatic malignant disease allows patients to benefit from a modality of treatment which can be both effective and minimally inconvenient when used appropriately.

Canada↗
PubMed1994

Endometrial cancer and abdominal wound recurrence.

A 65-year-old woman had a total abdominal hysterectomy and bilateral salpingo-oophorectomy through a Pfannenstiel incision for a Stage Ib, Grade 2 endometrial adenocarcinoma with extension to the middle third of the myometrium. No adjuvant treatment was given. She presented 7 years later with a large suprapubic mass and the entire lower central abdominal wall was removed and closed with Marlex mesh. Pathology revealed a moderately well-differentiated adenocarcinoma, very similar to the previous cancer with follow-up at 15 months revealing no evidence of recurrence. This case represents growth of implanted tumor cells in the incision that occurred 7 years previously at the time of an uneventful hysterectomy without tumor transgression. It is felt that there was intraoperative tumor cell extrusion through the cervical os with subsequent growth of viable tumor cells.

Abdominal Injuries↗
PubMed1992

Radiotherapy to the surviving kidney after unilateral nephrectomy in bilateral Wilms' tumour.

Despite an improving overall survival rate for children with Wilms' tumour, four out of seven patients with bilateral tumours died in the period from 1952 to 1960 and five out of eight died in the period from 1971 to 1989, at St Bartholomew's Hospital and the Hospital for Sick Children. More aggressive chemotherapy with both adriamycin and actinomycin D and concern over young age being predisposed to late radiation morbidity prompted us to keep radiotherapy dose prescriptions to the surviving kidney below the quoted renal radiation tolerance dose equivalent. In three long-term survivors treated with daily fractions up to 167 cGy and total doses of 1000-1200 cGy, we have found renal function and growth to be within the "normal" range at follow-up and the patients to be normotensive 6-8 years later. As four of the eight patients reported here died from local disease progression within the kidney (albeit despite slightly larger dose prescriptions), we discuss the potential for larger total doses to be delivered in this situation.

Child↗
PubMed1990

A pilot study of chemo-radiotherapy in advanced carcinoma of the vulva.

Advanced squamous cell carcinoma of the vulva (FIGO stages III and IV) has a poor cure rate even with exenterative surgery. We report a pilot study of combined pre-operative chemo-radiotherapy (CHT/RT) in all patients with advanced vulval carcinoma presenting to St Bartholomew's Hospital between July 1987 and March 1989. Twelve patients have been treated, of whom nine had primary lesions (four FIGO stage III and five stage IV) and three had recurrent disease after simple or radical vulvectomy. Seven patients were treated with an initial split course of CHT/RT: there was one treatment-related death and the others have all died following recurrence with a median disease-free survival of 5 months (range 3-12) and a median survival of 7 months (range 3-16). Five patients have received a continuous course of CHT/RT: one died before operation with pulmonary metastases, three patients are disease free at 6 to 9 months, and another patient has been treated with only palliative intent. Toxicity was acceptable in the continuous regimen and this treatment seems to have a promising role in the management of advanced carcinoma of the vulva. A review of the literature on combined therapy is presented.

Aged↗
PubMed1989

Platinum chemotherapy, radiotherapy and the inner ear: implications for "standard" radiation portals.

In this centre, platinum chemotherapy precedes radiotherapy in several primary malignancies arising in structures adjacent to the mastoid bone. The augmented ototoxicity of platinum and radiotherapy to fields encompassing the inner ear is exemplified by a case report. The order of administration may not be critical. This important toxicity, particularly for young patients, may be reduced by careful shielding considerations during planning of radiation portals, as exemplified in two further cases, and by carboplatin chemotherapy.

Adult↗
PubMed1988

Chemotherapy for poor risk germ cell tumours. An independent evaluation of the POMB/ACE regime.

We have evaluated the 7-drug, alternating, high-dose cisplatin regime for germ cell tumours, designated POMB/ACE, in 55 patients with advanced malignant teratomas and 5 patients with bulky metastatic seminomas. All of the latter and 5 of the teratoma patients had relapsed following radiotherapy, chemotherapy or both. The previously untreated teratoma patients included 13 whose tumours were extragonadal. The primary testicular tumour patients comprised 16 with large and 21 with very large volume metastases according to the Medical Research Council criteria. POMB/ACE is effective therapy for poor risk patients with germ cell tumours (including those with the most advanced disease, i.e. hepatic and cerebral metastases) and prolonged treatment after marker normality seems unnecessary. It is a complex regime with significant toxicity and cannot be recommended for the treatment of patients with germ cell tumours who have an excellent prognosis with simpler, shorter and less toxic treatment.

Antineoplastic Combined Chemotherapy Protocols↗