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Biomedical subjects

G Blackledge

Publications and source records attributed to G Blackledge.

At least 55 records · Page 3Linked to original sources
PubMed1989

Response of patients in phase II studies of chemotherapy in ovarian cancer: implications for patient treatment and the design of phase II trials.

Results using the same drug in phase II studies of treatment in ovarian cancer vary widely. An analysis of five phase II studies with a total of 93 patients was carried out to determine whether factors other than the efficacy of the drug affect response. The drugs for the phase II studies were chosen on the basis of in vitro activity or previous activity in humans. Univariate analysis showed that several factors were of significance in predicting response. The most significant was interval from the end of previous treatment to entry into a phase II study. Others were the original presenting stage of the patient, the second line treatment given and the best previous response to therapy. In multivariate analysis, however, only two factors were shown to be of importance which were interval and the FIGO stage of the patient. Using these two variables the discriminant analysis predicted 89% of those who did not respond and 75% of those who did, with an overall correct prediction of 85%. The importance of interval is emphasised by the observation that the response rate for those patients who progressed on treatment or who relapsed within 3-6 months of primary therapy had a response rate of less than 10%. Future phase II studies should probably exclude patients in this category, since the chance of their responding is very low.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Problems of peritoneal access in intraperitoneal treatment and monitoring of ovarian cancer.

A total of 154 peritoneal lavages was attempted through either a permanent (17) or a temporary percutaneous cannula (137) in 59 ovarian cancer patients undergoing intraperitoneal treatment or monitoring. Seven of the eight permanent catheters were removed because of complications; intraperitoneal adhesions were a major problem in this group. Overall, 137 temporary catheters were inserted (14G Venflon i.v. cannula in 119, Verres needle in 15, and a Trocath peritoneal dialysis catheter in 3 instances) but it was not possible to perform a peritoneal lavage in 42 (30%). Access to the peritoneal cavity was unsatisfactory on 29 (34%) occasions when a Venflon cannula was used, either because there was inadequate flow of lavage fluid into the peritoneal cavity or this was limited by pain. Perforation of the bowel occurred in 12 (9%) cases but there was no significant morbidity. Problems with achieving reliable peritoneal access using either permanent or temporary catheters may limit the potential advantages of the intraperitoneal route for treatment and monitoring.

Adult↗
PubMed1989

Urinary polyamine excretion patterns in patients with epithelial ovarian cancer.

Free and acetylated urinary putrescine, spermine and spermidine levels (UPA) and total polyamine excretion were measured by high-performance liquid chromatography in 57 patients with epithelial ovarian cancer (EOC) and 43 control patients. Mean UPA levels were higher and the number of abnormal UPAs per sample greater for cancer patients but maximum single UPA sensitivity was only 29%. No control subject had more than 2 abnormal UPA values compared with 42% of patients with EOC. Rising UPA levels reflected progressive disease in 83% of patients and fell with tumour response in 66%.

Adult↗
PubMed1989

Neoadjuvant (cytoreductive) chemotherapy combined with intervention debulking surgery in advanced, unresected epithelial ovarian cancer.

Thirty-six patients with epithelial ovarian cancer, incompletely resected at primary laparotomy, were treated with one of two intensive cis-platinum-based combination chemotherapy regimens. The intention was to perform further surgical debulking (intervention debulking surgery) after three cycles in patients responding to treatment. Intervention debulking surgery was carried out in 28 of 36 patients (78%) at a median interval of 12.7 weeks from primary diagnosis. Omentectomy and total abdominal hysterectomy were the most commonly performed procedures at intervention debulking. As a result of such surgery, 16 of the 28 women (57%) were left with no macroscopic residual disease, five (18%) had less than 1 cm, four (14%) less than 2 cm residuum, and three (11%) remained with more extensive disease. Post-intervention debulking surgical complications were few, with a median postoperative hospital stay of 10 days and a median interval of 21 days from debulking surgery to resumption of chemotherapy. Neoadjuvant (cytoreductive) chemotherapy combined with early secondary surgical debulking is feasible, with little severe morbidity, and can leave a high proportion of patients free of macroscopic disease. The effect of such a program on patient survival is now being tested in a randomized study.

Adult↗
PubMed1989

The role of ifosfamide in cervical cancer.

A series of phase II studies using ifosfamide as a single agent and in combination with cisplatin and bleomycin (BIP) in advanced and recurrent cervical cancer were coordinated at the West Midlands Cancer Research Campaign Clinical Trials Unit, Birmingham, UK. The aim of these studies was to identify single agents and combination regimens that might be of value for palliation and have potential for neoadjuvant and adjuvant therapy in primary treatment. Ninety-eight patients were studied. Seventy-nine patients with disease not amenable to radical local therapy were treated with single-agent ifosfamide or the BIP combination. In 30 patients treated with single-agent ifosfamide, ten objective responses (33%) were seen, with one complete response. In 49 patients treated with BIP, 34 objective responses (69%) were seen, with ten complete responses (20%). Eleven (79%) of 14 patients with primary inoperable disease had at least a 50% reduction in tumor bulk before radical local radiotherapy. Toxicity resulted in alopecia, nausea and vomiting, myelosuppression, infection, reduction in renal function, and disturbance of consciousness. There was no evidence that neoadjuvant chemotherapy enhanced the acute toxic effects of pelvic radiotherapy. These data indicate that ifosfamide is highly active in cervical cancer and that in combination with bleomycin and cisplatin, it can be used for effective palliation and cytoreduction in around 70% of patients. Ifosfamide-containing regimens have potential for use as neoadjuvant and adjuvant therapy in patients at high risk of recurrence with conventional treatment. These hypotheses are currently being tested in prospective randomized trials.

Adult↗
PubMed1988

Failure of second-look laparotomy to influence survival in epithelial ovarian cancer.

The survival benefit of second-look laparotomy after completion of primary chemotherapy in patients with epithelial ovarian cancer has been assessed in a prospective randomised trial of 166 patients. Patients were randomised into three groups. All were initially treated with cisplatin (100 mg/m2 x 5) after primary laparotomy. Group A (n = 53) was scheduled to have a second-look laparotomy, followed by cyclical oral chlorambucil. Group B (n = 56) was scheduled to have a second-look laparotomy, followed by total abdominal and pelvic irradiation, and group C (n = 57) received oral chlorambucil as for group A but had no second-look operation. With a median follow up of 46 months (range 21-64), no differences in survival were noted between the three groups. The median survival for group A was 21 months (95% CI 11-31 months), for group B 15 months (11-19), and for group C 17 months (8-26). Thus second-look laparotomy after completion of first-line single-agent cisplatin chemotherapy did not confer any survival benefit on patients with epithelial ovarian cancer.

Actuarial Analysis↗
PubMed1988

Pancreatic cancer.

Explore the source record for details and available documents.

Combined Modality Therapy↗
PubMed1988

Young age as a prognostic factor in cervical cancer: analysis of population based data from 10,022 cases.

The effect of young age on survival in cervical cancer is not fully known, although evidence has suggested that it is a poor prognostic factor and that young patients should therefore be treated differently from older patients. All 10,022 cases of invasive cervical cancer in the west Midlands during 1957-81, which comprised 10% of the cases in England and Wales, were analysed to determine the prognostic effect of age. Univariate analysis showed a median survival time of 54 months for all cases, with survival rates at five years of 69% for patients aged under 40 and 45% for those aged 40 or older (chi 1(2) (log rank) = 331.4; p less than 0.0001). This difference remained significant after stratification for stage (chi 1(2) (log rank) = 7.1; p = 0.008). Cox regression analysis with nine covariables, including age and year of registration, reaffirmed the importance of conventional prognostic factors such as stage of disease, size of tumour, state of lymph nodes, and differentiation of the tumour. After allowance was made for the effects of other prognostic factors young age was found to be a small but significant favourable factor that did not change during the period of the study. Estimated survival distributions obtained from the Cox model showed that for women presenting with the common characteristics associated with stage Ib disease who were treated with radical radiotherapy the survival rate at five years fell non-linearly from 71% in the group aged 25-29 to 65% in the group aged 65-69. Young age alone is not a reason to alter existing policies for treatment for patients with invasive cervical cancer.

Adenocarcinoma↗
PubMed1988

Maintenance chlorambucil after CVP in the management of advanced stage, low-grade histologic type non-Hodgkin's lymphoma. A randomized prospective study with an assessment of prognostic factors.

One hundred sixty-two patients with Stages III and IV non-Hodgkin's lymphoma of low-grade histologic type were treated with combination chemotherapy using cyclophosphamide, vincristine, and prednisolone (CVP) followed by radiotherapy to sites of previous bulk disease. The patients were randomized to receive either follow-up alone or "maintenance" chemotherapy with 2 years of intermittent chlorambucil. A complete remission was obtained in 56% of patients and the median survival was 64 months (median follow-up, 74 months). Multivariate analysis revealed stage (P less than 0.0001) and Karnofsky performance status (P = 0.021) to predict complete response (CR) and the achievement of a CR (P less than 0.0001), female sex (P = 0.008), the absence of bulk disease (P = 0.038) and low serum alkaline phosphatase (P = 0.002) to predict prolonged survival. The median relapse-free survival (RFS) of the complete responders was 41 months. A prolonged RFS was predicted by low stage (P = 0.014), low serum lactic dehydrogenase (LDH) (P = 0.045) levels, and by the administration of maintenance chlorambucil (P = 0.045). A prolonged survival of the complete responders was predicted by a low number of nodal sites of involvement with lymphoma at presentation (P = 0.022) and lack of liver involvement (P = 0.011). The administration of oral maintenance therapy with chlorambucil for a full 2 years was only possible in 38% of patients, mainly because of progression of disease and the induction of thrombocytopaenia, but despite this it prolonged the median RFS by 38 months and its use could be considered when future studies are being designed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

HPV 16 DNA in normal and malignant cervical epithelium: implications for the aetiology and behaviour of cervical neoplasia.

Southern blot hybridisation showed that cervical cancer biopsy specimens from 31 of 47 (66%, 95% confidence interval [CI] 52-80%) patients contained HPV 16 homologous DNA sequences, with evidence of integration of viral genome into host cell chromosomes in 7. Normal ectocervical biopsies from 9 of 26 (35%, 95% CI 16-53%) control women contained HPV 16 DNA, and none showed evidence of integration. HPV 16 DNA positivity did not correlate with marital or sexual history, parity, use of oral contraceptives, or smoking habits in cases or controls, or with outcome of treatment in cases. HPV 16 DNA positivity was found less frequently with age less than 40 years old than with age greater than 40 in both cases (p less than 0.05) and controls (p less than 0.01). After age-adjustment there was no significant difference between cases and controls in frequency with which HPV 16 DNA was found. These data suggest that the association between HPV 16 and cervical neoplasia is age-mediated and that the presence of the viral genome may not always warrant intervention.

Adenocarcinoma↗
PubMed1987

Cyclophosphamide versus ifosfamide: final report of a randomized phase II trial in adult soft tissue sarcomas.

Ifosfamide (IFOS) 5 g/m2 and its parent analog Cyclophosphamide (CYCLO) 1.5 g/m2 were studied in a randomized phase II study, accruing 171 patients with advanced soft tissue sarcoma. Both drugs were administered as 24 hr infusions, every 3 weeks, with comcomitant Mesna 400 mg/m2 i.v. bolus 4 hourly X 9 doses. Twenty-four patients were ineligible and 12 were not evaluable. The groups were well matched for age, previous chemotherapy (42% of the total) or radiotherapy, the presence of distant metastases and performance status, but there were more females (59% vs. 45%) in the IFOS arm. Among the 68 evaluable patients receiving IFOS, there were 2 CR, 10 PR (overall response 18%), 27 SD and 29 PD. For CYCLO, the corresponding results in 67 patients were 1 CR, 4 PR (overall response 8%), 23 SD and 39 PD. Using the chi-square test the P values for response rate and linear trend were 0.13 and 0.04 respectively. Response rates were higher for females (20% vs. 5%, P = 0.01) and patients who had not received previous chemotherapy (19% vs. 4%, P = 0.01). Fourteen of the 17 responses came from a group of 43 females, who had not received previous chemotherapy, for whom the overall response rate was 37.5%. Remissions were noted in only 4 histological subtypes (centrally reviewed material), i.e., 5 of 17 synovial sarcomas, 7 of 13 mixed mesodermal sarcomas and 2 of 7 fibrosarcomas. One of the 31 leiomyosarcomas responded to Cyclophosphamide. Durations of response did not differ significantly between the 2 arms--median 26, range 10-81+ weeks. Leucopenia was significantly more severe on CYCLO, particularly in patients who had received previous chemotherapy (P = 0.007). Serious infections occurred in approx. 7% of patients with no difference between the two drugs, although there was one toxic death on CYCLO. Nausea and vomiting were significantly worse on IFOS and alopecia, related in extent to dose, was seen in both arms. Other side-effects, such as hematuria or rises in serum creatinine and encephalopathy, were infrequent and mild. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination therapy.

Adolescent↗
PubMed1987

Speed of response to platinum-based chemotherapy: implications for the management of epithelial ovarian cancer.

Seventy-nine patients with evaluable epithelial ovarian cancer following primary laparotomy and treated with one of three primary cis-platinum-containing regimens were studied to determine the rate at which clinical cytoreduction occurred and whether a rapid response to treatment was of prognostic significance by improving progression free interval (PFI) or survival. A rapid response to treatment improved PFI in patients treated with single agent cis-platinum (P = 0.04) and increased survival in patients treated with a sequential cis-platinum based combination regimen (P = 0.03). The rate of cytoreduction was not a significant variable, however, in a multiple regression analysis of prognostic factors. Over 75% of all clinical responses, regardless of the regimen, had begun by the completion of the third course of chemotherapy. We conclude that response to active chemotherapy is a rapid phenomenon in ovarian cancer and this has important implications in both the decision to change drug therapy and the timing of further surgical effort.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Recurrent female pelvic cancer: assessment with transrectal ultrasonography.

Fifty-two women with symptoms or signs suggesting pelvic recurrence of biopsy-proved pelvic cancer were assessed in a prospective trial by clinical examination, transabdominal pelvic ultrasonography (TAU), computed tomography (CT), and transrectal pelvic ultrasonography (TRU). TRU significantly added to the information from TAU in the measurement of abnormalities on the pelvic sidewalls, and to TAU and CT in the measurement of abnormalities in the central and presacral regions of the pelvis. Results of this preliminary study suggest that TRU may provide information complementary to that from CT in women with suspected recurrence of gynecologic cancer.

Adult↗
PubMed1987

Phase II study of mitoxantrone in epithelial ovarian cancer.

Forty-six patients with advanced epithelial ovarian cancer were treated with mitoxantrone (14 mg/m2) given iv every 3 weeks. All patients had evaluable disease. Forty-one patients had had previous treatment, 38 with cisplatin. Twelve patients achieved partial response (two had had no previous treatment; ten had received previous treatment with cisplatin with or without other agents); two of the responders, both previously treated with cisplatin, achieved complete clinical remissions. Median duration of response was 24 weeks (range, 10-30). Toxicity was acceptable, with minimal subjective toxicity. Hematological toxicity was dose-limiting, but it was possible to increase the dose on one or more courses by 2 mg/m2 in 16 patients. The drug was given as a bolus, and there was no evidence of acute cardiac side effects. These data suggest that mitoxantrone has significant activity in epithelial ovarian cancer and deserves further study.

Adult↗
PubMed1987

Multicenter study of trilostane: a new hormonal agent in advanced postmenopausal breast cancer.

Trilostane, an inhibitor of the production of adrenal estrogens, was administered, together with dexamethasone, to 97 eligible postmenopausal women with advanced breast cancer. Seventy-four patients who had either received trilostane for a minimum of 10 weeks or whose disease had progressed while on trilostane before this period were assessed for tumour response. Eighteen patients (25%) had objective responses (two complete, 16 partial); a further 21 patients had stable disease. The response rate among all 97 patients, including those not treated for a minimum 10-week period, was 19%. Thirty-two of 97 patients reported adverse reactions which were attributed to trilostane and/or dexamethasone. Therapy was stopped for 15 patients, and the dose of trilostane was reduced for ten. Diarrhea was the commonest side effect, being reported in 16 patients, of whom nine stopped treatment. Trilostane, given with a corticosteroid, is an effective alternative hormonal agent acting by adrenal blockade for postmenopausal women with advanced breast cancer.

Breast Neoplasms↗