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R P Abratt

Publications and source records attributed to R P Abratt.

At least 19 recordsLinked to original sources
PubMed2001

Modeling tumor and treated lung volume influences in the irradiation of non-small-cell lung cancer patients.

PURPOSE: The proposal of a hypothetical model in patients treated by irradiation for non-small-cell lung cancer show the dependence of local tumor control and patient cure rates on the volume of tumor and irradiated lung tissue. RESULTS: The local tumor control rates from conventional doses of irradiation decreases and the metastases rate increases with the tumor volume. Dose escalation will increase the potential cure rates (product of the local control and the freedom from metastases rates). Any potential gain will, however, be modified by the effect of irradiation on normal lung. Studies indicate that this is dependent on the volume of lung irradiated above a threshold dose. CONCLUSION: A clinically significant and measurable increase in cure rates from dose escalation may be seen in smaller tumors. This is unlikely to occur in larger tumors, although dose escalation to a restricted volume combined with effective systemic chemotherapy is one of the options that may be explored. The relevance of modeling and future studies of tumor and normal tissue volume effects, will increase from the widespread usage of the dose-volume histogram.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Combined cisplatin and gemcitabine for non-small cell lung cancer: influence of scheduling on toxicity and drug delivery.

The scheduling of cytotoxic chemotherapy has important bearing on the toxicity and ability to deliver chemotherapy at or close to full dose. We report new data on the influence of different schedules of cisplatin and gemcitabine on toxicity and drug delivery in phase II studies of non-small cell lung cancer. Patients in six phase II studies had standard entry criteria for advanced non-small cell lung cancer. Whereas gemcitabine was given on days 1, 8, and 15 of a 28-day cycle in all these studies, the scheduling of cisplatin varied and was given either on day 1, day 2, day 15 (in two studies), or days 1, 8, and 15 (in two studies). The protocol dose per infusion for gemcitabine was 1,000 mg/m2 (five studies) and 1,500 mg/m2 (one study); for cisplatin, it was 100 mg/m2 when given once per cycle and 30 mg/m2 when given on days 1, 8, and 15. Similar dose reduction schedules were implemented in the event of grade 3 or higher drug toxicity for all studies except for the day 1 cisplatin study, in which the dose was omitted for grade 2 thrombocytopenia. Nonhematologic toxicity was very low. Hematologic toxicity was moderate, and in patients who developed grade 3 or 4 toxicity, there was no hemorrhage from thrombocytopenia and neutropenic sepsis was rare. The incidence of grade 3 or 4 thrombocytopenia with the day 1, day 2, day 15 (two studies combined), and days 1, 8, and 15 (two studies combined) cisplatin regimens was 50%, 52%, 26%, and 38%. The incidence of grade 3 or 4 neutropenia with these four regimens was 51%, 37%, 56%, and 49%, respectively. Although the hematologic toxicity might appear relatively similar, it represents the toxicity at the administered rather than the intended (protocol) dose, because drug delivery was reduced or omitted in the event of grade 3 or 4 toxicity. Differences between the schedules are revealed by analysis of the actual dosages delivered. The median dosage of gemcitabine per scheduled infusion was statistically higher with the day 15 cisplatin regimens (combined) compared with any of the other regimens treating at 1,000 mg/m2 (P < .003, z-score). The dose with the day 1, day 2, day 15, and days 1, 8, and 15 cisplatin regimens was 664, 829, 889, and 774 mg/m2, respectively. Both the percentages of cycles in which gemcitabine infusions were given at full dose and in which there were no omissions of gemcitabine infusions (including infusions with dose reductions) were statistically higher in the day 15 cisplatin regimen than with any of the other regimens (P < .0001, chi-square test). The percentage of cycles containing full-dose gemcitabine with the day 1, day 2, day 15, and days 1, 8, and 15 cisplatin regimens was 24%, 44%, 75%, and 46%, respectively. The percentage of cycles in which there were no omissions of gemcitabine infusions for the four regimens above was 32%, 55%, 83%, and 72%, respectively. Apart from the once-weekly regimen (days 1, 8, and 15) in which the protocol gemcitabine dose was 1,250 mg/m2, the day 15 cisplatin schedule allowed for the highest median concentration of gemcitabine. More importantly, the day 15 cisplatin schedule provided the longest duration of gemcitabine exposure, which is particularly important for its activity as gemcitabine is a phase-specific agent. The day 15 cisplatin schedule is associated with the best dose intensity and the longest median duration of exposure to gemcitabine, and best meets the goal of administering both agents at full doses in combination.

Adult↗
PubMed1998

Radical cystectomy for invasive bladder cancer--a local experience.

OBJECTIVES: The aim of this study of patients undergoing cystectomy for invasive transitional cell carcinoma of the bladder was to compare clinical and pathological staging and to review factors that predict survival. PATIENTS: Sixty-three patients (73% male) underwent radical cystectomy between January 1988 and February 1994. The mean age was 61 years (range 33-77 years). RESULTS: Of the patients 14% had clinical and 24% pathological stage T1 disease; figures for T2 disease were 24% and 6%, respectively, for T3 disease 46% and 45%, and for T4 disease 16% and 25%. For T1 and T4 disease the clinical stage predicted the pathological stage in over 80% of cases, and for patients with T3 disease the predictive value of clinical staging was 68%; in no patient with clinical stage T2 disease was this confirmed at cystectomy. The prevalence of tumour infiltration of the lymph glands on histological examination of the cystectomy specimen correlated more closely with pathological stage than with clinical stage. For clinical and pathological staging, respectively, the prevalences were 0% and 0%, for T1, 27% and 0% for T2, 20% and 29% for T3, and 40% and 38% for T4. The overall survival rate (life-table method) was 33% at a median follow-up of 42 months in the surviving patients. No patient with tumour infiltration of the lymph glands survived. Survival also correlated more closely with pathological than with histological stage. For clinical and pathological stage T1 disease the 5-year survival rates were 73% and 91%, respectively; for T2 the rates were 27% and 75%, for T3 32% and 31%, and for T4 28% and 29%. The operative mortality rate was 2% and the rate of recurrence of local disease 10%. CONCLUSIONS: Survival after cystectomy correlates more closely with pathological than with clinical stage of disease. The accuracy of clinical staging in T2 disease is poor. Cystectomy is the standard against which other treatments for bladder cancer must be measured.

Adult↗
PubMed1997

Weekly gemcitabine with monthly cisplatin: effective chemotherapy for advanced non-small-cell lung cancer.

PURPOSE: The aim of this study was to examine the efficacy of a regimen of initial gemcitabine followed by cisplatin in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-three patients (36 men and 17 women; age range, 35 to 74 years) were enrolled. Patients had bidimensionally measurable disease. Gemcitabine (phase-specific agent) was administered on days 1, 8, and 15 at a dose of 1,000 mg/m2. Cisplatin (cycle-specific agent) was administered on day 15 (100 mg/m2). Chemotherapy was administered in 28-day cycles. RESULTS: Of 53 patients enrolled, 50 were assessable for response. The overall response rate was 52%. There were two complete responses (4%) and 24 partial responses (48%). The median survival duration was 13 months and the 1-year survival rate was 61%. The regimen was generally well tolerated. World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 38.8% and 19.2% of patients, respectively. Grade 3 and 4 thrombocytopenia occurred in 13.3% and 7.7% of patients, respectively. Most patients experienced mild nausea and vomiting. Few patients had hair loss and oral toxicity was mild. Relatively few patients required dose modifications for any of the three weekly doses of chemotherapy. For the first two cycles of chemotherapy, the dose-intensity per infusion was 947 mg/m2 for gemcitabine and 85 mg/m2 for cisplatin. CONCLUSION: This regimen of gemcitabine and cisplatin was effective, with high response and survival rates and few dosage modifications during its administration. Prospective randomized studies with other cisplatin-based combination chemotherapy regimens are indicated.

Adult↗
PubMed1997

Gemcitabine in the treatment of elderly patients with advanced non-small cell lung cancer.

Gemcitabine is active against non-small cell lung cancer (NSCLC), with single-agent response rates of 20% or more in previously untreated patients. Its mild toxicity profile suggests that it should be well tolerated by older patients. To assess the impact of age on the efficacy and tolerance of gemcitabine, the results of four phase II trials of single-agent gemcitabine for the treatment of NSCLC were analyzed retrospectively. Starting doses for gemcitabine ranged from 800 to 1,250 mg/m2/wk, and in all studies gemcitabine was administered weekly for 3 weeks followed by a 1-week rest period. Response rates, toxicity, and dose delivery were compared for two age groups, less than 65 years (255 patients) or > or = 65 years (105 patients). The pretreatment characteristics for both patient groups were well balanced. Overall response rates were 16% and 24% for the younger and older patients, respectively (P = .072). Median survival and 1-year survival rates were 8.1 months and 27% and 9.1 months and 36%, respectively, for patients aged less than 65 years and > or = 65 years. Hematologic and nonhematologic toxicities were similar for both age groups. The number of cycles associated with dose reductions or dose omissions and the mean number of treatment cycles administered were also similar. In summary, gemcitabine is active and well tolerated in elderly patients with NSCLC, and is a promising new alternative for the treatment of this patient population.

Aged↗
PubMed1997

Weekly gemcitabine and monthly cisplatin for advanced non-small cell lung carcinoma.

Most chemotherapy for non-small cell lung cancer (NSCLC) currently includes combination chemotherapy based on cisplatin. Gemcitabine is a nucleoside analog with demonstrated activity against NSCLC, yet it has low toxicity. This phase II study was designed to examine the efficacy of a combination chemotherapy regimen consisting of gemcitabine followed by cisplatin. The patient population comprised 53 patients with pathologically confirmed locally advanced or metastatic NSCLC. Gemcitabine 1,000 mg/m2 was administered on days 1, 8, and 15 and cisplatin 100 mg/m2 was given on day 15. Chemotherapy was administered every 28 days. Of the 50 patients evaluable for response, there were two complete responses (4%) and 24 partial responses (48%). The median duration of response was 8.5 months, median survival was 13 months, and the 1-year survival rate was 61%. The regimen was generally well tolerated. World Health Organization grade 3 leukopenia occurred in 28.8% of patients, while grade 3 and 4 neutropenia occurred in 38.8% and 19.2% of patients, respectively. Grade 3 and 4 thrombocytopenia was seen in 13.3% and 7.7% of patients, and grade 3 and 4 anemia occurred in 11.5% and 1.9% of patients, respectively. Alopecia and oral toxicity was mild, although most patients experienced mild nausea and vomiting. Relatively few patients required dose modifications for any of the three weekly doses of chemotherapy. We conclude that the combination of gemcitabine and cisplatin is an effective regimen for NSCLC, resulting in high response and survival rates. Additional prospective randomized studies with other cisplatin-based combination chemotherapy regimens are warranted.

Adult↗
PubMed1997

Primary chemotherapy for stage 2 testis cancer.

To evaluate the efficacy and toxicity of primary chemotherapy in patients with stage 2 (retroperitoneal lymph node metastases) testis cancer, 20 consecutive patients referred to Groote Schuur Hospital between September 1992 and March 1994 were reviewed. There were 10 patients with non-bulky non-seminomatous germ cell tumour (NSGCT), 5 with bulky NSGCT and 5 with bulky seminoma. The treatment regimen consisted initially of 4 cycles of cisplatin, etoposide and bleomycin. Patients with NSGCT and a residual mass after chemotherapy subsequently underwent retroperitoneal lymph node dissection (RPLND) and those with seminoma underwent a low dose of irradiation to the mass. In 7 (70%) of the 10 patients with non-bulky NSGCT, there was a complete response to chemotherapy and 3 patients underwent limited RPLND. One patient relapsed at follow-up but remains clear of disease after salvage therapy. The survival rate is 100% at a median follow-up of 60 months (range 12-143 months). In 5 patients with bulky NSGCT there was no complete response to chemotherapy. Three have undergone limited RPLND. The survival rate is 52% at a median follow-up of 130 months (range 108-152 months). In 5 patients with bulky seminomas, the survival rate is 100% at a median follow-up of 55 months (range 29-92 months). Toxicity has been modest except for 1 patient who died postoperatively in the early part of the study. Four patients have fathered children after treatment. We conclude that primary chemotherapy is the treatment of choice for patients with stage 2 testis cancer.

Adolescent↗
PubMed1995

The effect of irradiation on lung function and perfusion in patients with lung cancer.

PURPOSE: To prospectively study the changes in lung function in patients with lung carcinoma treated with relatively high doses of irradiation. METHODS AND MATERIALS: Lung function was assessed prior to and at 6 and 12 months following radiation therapy by a clinical dyspnea score, formal pulmonary function tests (lung volume spirometry and diffusion capacity) as well as an ipsilateral hemithorax lung perfusion scan. Changes in dyspnea score were evaluated by the chi-square and the Fishers exact test. Changes in formal lung function tests were compared with the t-test for dependent data and correlations with the t-test for independent data. Fifty-one patients were entered into the study. There were 42 evaluable patients at 6 months after irradiation and 22 evaluable patients at 12 months after irradiation. RESULTS: A worsening of dyspnea score from 1 to 2, which is clinically acceptable, occurred in 50% or more of patients. However, a dyspnea score of 3, which is a serious complication, developed in only 5% of patients. The diffusion capacity (DLCO) decreased by 14% at 6 months and 12% at 12 months) (p < 0.0001). The forced vital capacity and total lung capacity decreased between 6% and 8% at 6 months and 12 months, which was statistically significant. The forced expiratory volume in 1 s decreased between 2 and 3% at 6 month and 12 months, which was not statistically significant. The ipsilateral hemithorax perfusion decreased by 17 and 20% at 6 and 12 months (p < 0.0001). There was no correlation between the initial hemithorax perfusion, or its decrease at follow up and the decrease in DLCO. CONCLUSION: Lung irradiation results in some loss of lung function in patients with lung cancer with a projected survival of 6 months or more. The pretreatment DLCO assessment should be useful in predicting clinical tolerance to irradiation.

Adult↗