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Biomedical subjects

M E Gore

Publications and source records attributed to M E Gore.

At least 55 records · Page 3Linked to original sources
PubMed1999

Delayed haemolytic transfusion reaction caused by anti-M antibody in a patient receiving interleukin-2 and interferon for metastatic renal cell cancer.

Anti-M is usually a naturally occurring cold-reactive immunoglobulin M (IgM) antibody, often with an immunoglobulin G (IgG) component, and is seldom implicated in delayed haemolytic transfusion reactions (DHTR). However, cases have been reported. In the majority, a DHTR is not suspected until further blood is requested and a new antibody is detected on pretransfusion testing. We describe the case of a young man receiving therapy with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) for metastatic renal cell cancer who developed a clinically suspected DHTR that was confirmed serologically to be caused by anti-M, reactive at 37 degrees C. We discuss the possible role of his biochemotherapy in the development of the DHTR.

Adult↗
PubMed1999

New approaches to the systemic treatment of melanoma.

Metastatic melanoma is an incurable condition with a median survival of about 6 months. Chemotherapy can result in objective tumour responses but only in a minority of cases and remissions are short-lived, 3-6 months. DTJC is the most active single agent with response rates of 15-20% and although combination chemotherapy can result in higher response rates there is no response duration or survival advantage. Phase II studies have suggested that combining chemotherapy with biological response modifiers may result in higher response rates, in the order of 50% and the results of two large randomized trials investigating this approach are awaited. Adjuvant trials currently focus on interferon and/or vaccine strategies. Further data are required before any adjuvant treatment can be regarded as standard.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Gastrostomy tubes in patients with recurrent gynaecological cancer and intestinal obstruction.

OBJECTIVE: Women with recurrent gynaecological cancers who are not suitable for exenterative surgery commonly present with gastrointestinal dysfunction. This paper is a retrospective review of the use of gastrostomy tubes in such women. METHODS: We performed a chart review of women with recurrent gynaecological cancer who had a gastrostomy tube placed between January 1991 and April 1998. RESULTS: Thirty-nine women (mean age 53.2 years, range 17-82) had a gastrostomy tube placed. Twenty-eight (72%) had ovarian cancer, eight (21%) had cervical cancer, two had endometrial cancer and one had vaginal cancer. In 14 women a gastrostomy tube was placed as the sole procedure for palliation (11 elective, 3 emergency). In the remaining 25 women, who underwent major surgery, a gastrostomy tube was placed in anticipation of, or in the presence of, significant intestinal distension and expected prolonged post-operative ileus. Eleven women (28%) died without leaving hospital after their operation (median 11 days, range 2-36). All but one of the 28 women who left hospital had satisfactory oral intake. Twenty-one women (54%) died with the gastrostomy tube in place (median 28 days, range 2-157) and 18 (46%) had the gastrostomy tube removed (median 14.5 days, range 9-180), 13 of whom (33%) have since died (median 167 days, range 77 days-7 years). Five women (13%) are alive (median 2.2 years, range 10 months-4.5 years). There were no problems which required the gastrostomy tube to be removed. CONCLUSION: Gastrostomy tubes have an important role in the treatment of women with recurrent gynaecological cancer, allowing gastric drainage and decompression without the disadvantages of nasogastric tubes.

Acute Disease↗
PubMed1999

Comparison of standard and CA-125 response criteria in patients with epithelial ovarian cancer treated with platinum or paclitaxel.

PURPOSE: To assess CA-125 as a measure of response in patients treated with paclitaxel. PATIENTS AND METHODS: One hundred forty-four patients treated with paclitaxel derived from four different trials and 625 patients treated with platinum from two trials were analyzed using precisely defined 50% and 75% reductions in CA-125. The standard and CA-125 response rates to paclitaxel and platinum were compared. In addition, we analyzed individual patient groups in which there was a difference in response according to the two response criteria. RESULTS: Patients with stable disease as determined by standard criteria who were treated with platinum and responded according to CA-125 criteria have an improved median progression-free survival compared with patients with stable disease who did not respond according to CA-125 criteria (10.6 v 4.8 months; P<.001). Standard and CA-125 response rates for patients treated with platinum (58.93% v 61.31%, respectively) and paclitaxel (30.65% v 31.67%, respectively) were very similar, as were rates of false-positive prediction of response by CA-125 (platinum 2.2% and paclitaxel 2.9%). Responders to paclitaxel had a significantly improved progression-free survival compared with non-responders by both standard criteria (median progression-free survival, 6.8 v 2.5 months; P<.001) and CA-125 criteria (median progression-free survival, 6.8 v 3.4 months; P<.001). CONCLUSION: Forassessing activity of therapy for ovarian cancer, these data show that precise 50% or 75% CA-125 response criteria are as sensitive as standard response criteria. We propose that they may be used as a measure of response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer. Sensitivity is maintained whether patients are treated with platinum or paclitaxel.

Antineoplastic Agents↗
PubMed1999

Natural history of stage IV epithelial ovarian cancer.

PURPOSE: In this report we present the natural history, prognostic factors, and therapeutic implications of stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: We reviewed 192 patients with stage IV EOC as defined in 1985 by the International Federation of Gynecology and Obstetrics. RESULTS: The site of stage IV-defining disease was cytologically positive pleural effusion in 63 patients, liver in 50 patients, lymph nodes in 26 patients, lung in six patients, other sites in 15 patients, and disease at multiple stage IV-defining metastatic sites in 32 patients. Surgery was performed before chemotherapy in 169 patients; 25 patients (14.8%) were left with only microscopic residual disease or less than 2 cm of macroscopic residual disease. The overall response rate to chemotherapy was 56%; the complete response rate was 18%. The median progression-free survival was 7.1 months, and the median overall survival was 13.4 months. The median overall survival of patients with positive pleural effusions only was 13.4 months as compared with 10.5 months for patients with visceral disease only, but this difference was not statistically significant. The 5-year survival rate was 7.6%, with only six patients surviving more than 5 years. Univariate and multivariate analysis showed that two parameters were associated with a shorter survival time: visceral involvement (lung or liver) and diagnosis before 1984. CONCLUSION: Patients with stage IV EOC initially respond to chemotherapy as often as those with less advanced disease, but the long-term prognosis is very poor. The size of residual disease is not a prognostic factor in this group of patients, and, therefore, the role of debulking surgery in these patients needs to be reconsidered.

Adult↗
PubMed1998

Granulosa cell tumours of the ovary: demographics, survival and the management of advanced disease.

Ovarian granulosa cell tumours (OGCT) are rare, accounting for only 3%-5% of primary ovarian tumours. As a result of oestrogen production OGCTs tend to present with early stage disease, which has a good prognosis. For patients with advanced disease, surgery and radiotherapy have been the major modalities of treatment. More recently, platinum-based chemotherapy has been shown to have important activity in advanced disease. In this retrospective study, we have reviewed the results of 62 patients who were treated for adult OGCT at the Royal Marsden Hospital between 1969 and 1995, with particular emphasis on the management of advanced disease. The median age at primary diagnosis was 53 years (range 13-77). Sixty-one per cent of these patients had Stage I disease, 21% Stage II disease, 16% Stage III and 2% Stage IV. Stage I patients had a good prognosis with 5- and 10-year overall survival rates of 95% and 90%. Eleven Stage I patients received adjuvant pelvic radiotherapy, with no apparent benefit to recurrent rate or overall survival. Disease progression occurred in 40% of Stage I patients at a median interval of 76 months (range 12-240), and in 62% of the Stage II patients, at a median interval of 31 months (range 2-57). The median interval from progression of Stage I/II disease to death was 22 months (range 3-144). For patients with inoperable disease, radiotherapy produced a number of long-term remissions with an overall response rate of 50%. Platinum-based chemotherapy also appears active, with responses documented in four out of five patients treated with the PVB regimen (cisplatin, vinblastine, bleomycin) as first line therapy. There were no responses documented to non-platinum chemotherapy or to hormonal manipulation. The results from this study confirm the activity of platinum-containing chemotherapy regimens in OGCT and support the need for further trials to optimize the management of this rare tumour.

Adolescent↗
PubMed1998

Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and interleukin (IL-2) in patients with metastatic melanoma.

The purpose of this study was to evaluate in a randomized phase II trial the efficacy and toxicity of combination biochemotherapy compared with chemotherapy alone in patients with metastatic melanoma. Sixty-five patients with metastatic melanoma (ECOG performance status 0 or 1) were randomized to receive intravenous BCNU 100 mg m(-2) (day 1, alternate courses), cisplatin 25 mg m(-2) (days 1-3), DTIC 220 mg m(-2) (days 1-3) and oral tamoxifen 40 mg (BCDT regimen) with (n = 35) or without (n = 30) subcutaneous interleukin 2 (IL-2) 18 x 10(6) iu t.d.s. (day - 2), 9 x 10(6) iu b.d. (day - 1 and 0) and interferon 2 alpha (IFN-alpha) 9 MU (days 1-3). Evidence for immune activation was determined by flow cytometric analysis of peripheral blood lymphocytes. Treatment was repeated every 4 weeks up to six courses depending on response. The overall response rate of BCDT with IL-2/IFN-alpha was 23% [95% confidence interval (CI) 10-40%] with one complete response (CR) and seven partial responses (PR), and for BCDT alone 27% (95% CI 12-46%) with eight PRs; the median durations of response were 2.8 months and 2.5 months respectively. Sites of response were similar in both groups. There was no difference between the two groups in progression-free survival or overall survival (median survival 5 months for BCDT with IL-2/IFNalpha and 5.5 months for BCDT alone). Although 3 days of subcutaneous IL-2 resulted in significant lymphopenia, evidence of immune activation was indicated by a significant rise in the percentage of CD56- (NK cells) and CD3/HLA-DR-positive (activated T cells) subsets, without any change in the percentage of CD4 or CD4 T-cell subsets. Toxicity assessment revealed a significantly higher incidence of severe thrombocytopenia in patients treated with combination chemotherapy than with chemotherapy alone (37% vs 13%, P = 0.03) and a higher incidence of grade 3/4 flu-like symptoms (20% vs 10%) and fatigue (26% vs 13%). The addition of subcutaneous IL-2 and IFNalpha to BCDT chemotherapy in a randomized phase II trial resulted in immune activation but did not improve response rates in patients with metastatic melanoma, and indeed may increase some treatment-related toxicity.

Adolescent↗
PubMed1997

The significance of paracardiac lymph node enlargement in ovarian cancer.

The computed tomography (CT) scans of 78 patients with stage II, stage III and relapsed stage I ovarian carcinoma were reviewed in order to identify the incidence of enlarged paracardiac lymph nodes in this disease, recognize their association, if any, with peritoneal metastases and establish whether they had any bearing on progression free interval and survival. Twenty-two patients (28%) were found to have enlarged paracardiac nodes, nine at initial presentation and a further 13 during the course of follow-up. The association between paracardiac node enlargement and peritoneal metastases was found to be highly significant. Thirty per cent of 27 patients with peritoneal metastases at presentation were found to have enlarged paracardiac nodes whereas of the 51 patients without peritoneal dissemination only 2% had enlarged paracardiac nodes (P < 0.001). In order to determine whether paracardiac nodal status had any independent prognostic value, multivariate analysis using Cox's regression was performed. When status at presentation was considered, the presence of enlarged paracardiac lymph nodes was found to be an independent predictor for survival. (Hazard ratio 3.70, 95% confidence interval (1.18-11.6), P < 0.04.) The hazard ratio for paracardiac nodal status with respect to progression free survival was not significant but in the expected direction. (Hazard ratio 1.85 (0.65-5.25).) When time-dependent covariate analysis was applied, paracardiac nodal status and peritoneal metastases status were found to be independent predictors for both progression free survival and overall survival. The presence of peritoneal metastases indicated a poorer prognosis than the presence of paracardiac lymph nodes, the hazards ratios for progression free survival were 12.9 and 2.58, respectively, and those for survival were 20.7 and 3.62, respectively. We have demonstrated that the presence of paracardiac lymph node enlargement is a significant adverse prognostic factor for both progression free interval and survival. The diagnosis of involved paracardiac lymph nodes is important as it can define patients having stage IV as opposed to stage III disease.

Adult↗
PubMed1997

The natural history and management of Merkel cell carcinoma of the skin: a review of 22 patients treated at the Royal Marsden Hospital.

Merkel cell carcinoma is a rare skin malignancy, which primarily affects the elderly. Currently, there is only limited data on the natural history of this condition and no consensus on its optimum management. We have reviewed the natural history and management of 22 patients with Merkel cell carcinoma, who were treated at the Royal Marsden Hospital between 1985 and 1994. The median age at diagnosis was 75 years (range 55-96), with the head and neck region being the most common site of disease (nine patients: 41%). Seventeen patients (77%) presented with skin disease, three (14%) with regional lymphadenopathy and two (9%) with metastatic disease. Of the Stage I patients, 41% developed local recurrence postoperatively at a median time to relapse of 12 months. Those with head and neck disease had the highest risk of local recurrence, which occurred in 62.5% of this group. Stage I patients also had a high risk of disease progression, with 53% developing regional lymphadenopathy or visceral metastases. The median survival for all disease stages was 47 months. The treatment of unresectable primary or recurrent disease with radiotherapy led to valuable long term control in four of nine patients treated. Six courses of chemotherapy were administered; one brief complete response was observed, occurring in a patient treated with cyclophosphamide, vincristine and doxorubicin. The data in this study confirms the predilection for the elderly and the aggressive nature of Merkel cell carcinoma, with only four of 17 Stage I patients remaining disease free. To clarify the role of adjuvant postoperative radiotherapy and to establish the appropriate use of chemotherapy in metastatic spread of this rare malignancy will require further studies with multicentre cooperation.

Aged↗
PubMed1997

A phase II study of continuous infusional 5-fluorouracil (5-FU) and subcutaneous interleukin-2 (IL-2) in metastatic renal cancer.

In this study, the safety with efficacy of infusional 5-fluorouracil (5-FU) (200 mg/m2/day) combined with subcutaneous interleukin-2 (IL-2) (9-27 x 10(6) IU/day) was investigated in patients with metastatic and renal cancer. In the 24 patients evaluated, the overall response rate was 17% (1 CR, 3 PR). The major toxicity was the vascular leak syndrome (VLS) which required inotrope support in 18% of treatment cycles. Other common systemic toxicities were vomiting, oedema and malaise (grades 1 and 2). There was no enhanced or novel toxicity from the combination of drugs. Based on this study, it will be feasible to use infusional chemotherapy with other cytokine combinations.

Adult↗
PubMed1997

Differential responses to chemoimmunotherapy in patients with metastatic malignant melanoma.

An open, multicentre non-randomised study was performed to evaluate the activity and toxicity of combination chemoimmunotherapy, consisting of cisplatin, interleukin-2 and interferon-alpha, in metastatic malignant melanoma. Between March 1992 and September 1993, 28 patients with pathologically proven metastatic malignant melanoma, bidimensionally measurable disease and an Eastern Co-operative Oncology Group score < or = 1 were treated with the combination chemoimmunotherapy. The regimen consisted of cisplatin (100 mg/m2 on day 0), interleukin-2 (Proleukin, Chiron, Middlesex, U.K.) 18 x 10(6)IU/m2/d continuous intravenous infusion on days 3-7 and 17-22, with interferon-alpha (Roferon-A, Roche, Hertfordshire, U.K.) 9 x 10(6) U/d subcutaneously on days 3, 5, 7, 17, 19, 21 during the interleukin-2 infusions. The treatment cycle lasted 28 days. Among 27 assessable patients, 5 patients achieved partial responses, for an overall response rate of 18% (95% CI 6-37%). Median progression-free survival was 44 days (range 8-279) and median overall survival was 264 days (range 41-1432). Differential responses were noted in 41% of patients and responses were more frequent in non-visceral disease (skin, lymph node and soft tissue disease) (P = 0.04). These results indicate that differential responses to chemoimmunotherapy are common in patients with metastatic melanoma. This may account for the broad range of response rates reported in the literature.

Adult↗
PubMed1997

Cisplatin and 5-fluorouracil for symptom control in advanced salivary adenoid cystic carcinoma.

Adenoid cystic carcinoma is a relatively rare tumour which arises in the parotid and submandibular salivary glands. Initial management is surgical, often with post-operative radiotherapy, but local relapse is common and distant metastasis not infrequent. Chemotherapy is generally reserved for cases where symptoms are not controlled by other means, since the tumour is slow growing and the response rate frequently disappointing. Cisplatin and 5-fluorouracil (5-FU) both show single agent activity in this disease but had not been previously investigated in combination. All patients referred for palliative chemotherapy of metastatic, symptomatic, histologically confirmed adenoid cystic carcinoma between November 1990 and February 1994 were considered for this study. The drugs were administered as follows: cisplatin 100 mg/m2 with appropriate pre- and post-hydration and 5-FU on a 4-day schedule of 1 g/m2/day. A total of 11 patients (7 male, 4 female) with median age 53 years (range 34-69) received 46 courses of chemotherapy (median four, range one to six). All patients had prior surgery and 8 had previously received radiotherapy. There were no objective responses of > 50% reduction in tumour size. 3 patients had a minor response and two progressed on treatment. The symptomatic response rate, however, was 64%, which compares favourably with other previously reported regimens. Toxicity was manageable. The median time to tumour progression was 9 months (range 0-38) and median survival was 12 months (range 1-65). This cisplatin/5-FU regimen would appear to produce a low rate of objective response but useful palliative benefits in advanced symptomatic adenoid cystic carcinoma. Prior series suggest that a higher objective response rate may be possible with a platinum/anthracycline/fluorouracil combination, and investigation of such a regimen is warranted.

Adult↗
PubMed1997

Chemotherapy for symptom control in recurrent squamous cell carcinoma of the head and neck.

BACKGROUND: The role of chemotherapy in patients with recurrent squamous cell carcinomas of the head and neck (SCCHN) is unclear. The aim of this study was to assess the ability of combination chemotherapy to control symptoms in this setting. PATIENTS AND METHODS: Using a prospectively accrued database all patients referred for chemotherapy with symptomatic relapse following surgery were identified. Objective response was recorded using standard criteria and maximum symptom response was assessed retrospectively from case notes using a published scoring scale. RESULTS: A total of 57 (median age 56, range 37-85) patients were studied who had received mainly cisplatin/5-fluorouracil combinations. Thirty-seven had previously received radiotherapy. Fifty-two patients had evaluable disease; 18 (35%) had objective responses (14 PRs and 4 CRs). There were a total of 103 symptoms recorded with eight different individual symptoms. Forty-four (43%) symptoms improved on treatment, 52 (50%) were unchanged and 7 (7%) worsened. The number of patients with improvement in the most frequently recorded symptoms were as follows: pain 11/28 (39%), swelling 12/23 (52%) and dysphagia 6/18 (33%). Sixty-seven percent of patients with objective response also had an improvement in their symptoms but a significant proportion (33%) of non-responders had a symptomatic response. Lack of objective response was not correlated with worsening symptoms. Grade 3/4 toxicity was uncommon (6%-17%) and there were no toxic deaths. A majority of patients (82%) experienced either no change or an improvement in performance status. CONCLUSION: These results demonstrate that chemotherapy improves many of the symptoms associated with recurrent SCCHN, without deterioration in performance status. Symptomatic improvement is more likely if there is evidence of significant tumour shrinkage, but even non-responding patients can benefit.

Adult↗
PubMed1997

Single-agent paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. London Gynaecological Oncology and North Thames Gynaecological Oncology Groups.

The aim of this study was to evaluate the efficacy of high-dose paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. Paclitaxel was administered intravenously over 3 h at a dose of 225 mg m(-2) on a 21-day cycle for six courses. Thirty-six patients were entered into this study; all 36 were assessed for toxicity and 33 patients were evaluable for response. One patient had a complete response and 12 patients had partial responses (overall response rate 39.4%, 95% CI 23-58%). The overall median duration of response was 9 months (range 3.5-23+ months). The response rate to carboplatin following failure of paclitaxel within 1 year of stopping therapy was 57% (four out of seven patients). The median survival of patients was 17.2 months. The main toxicity encountered was neutropenia which was WHO grade 3 in 11 patients (31%) and WHO grade 4 in seven patients (19%). Granulocyte colony-stimulating factor (GCSF) was not given to any patient during the study. Other toxicities were: grade 3/4 infection (11%) and nausea and vomiting (11%); grade 3 bone pain (22%), fatigue (14%), diarrhoea (3%), myalgia/arthralgia (3%) and dry eyes (3%). Transient peripheral neuropathy occurred in 16 patients (44%), and alopecia was encountered in most patients (grade 2/3, 78%). Paclitaxel given at 225 mg m(-2) to patients with stage IV epithelial ovarian cancer is active, well tolerated and does not require GCSF support.

Adult↗
PubMed1997

Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer.

A combination of platinum and a taxane is regarded by many as the optimum treatment for advanced epithelial ovarian carcinoma. A recent meta-analysis has suggested that the addition of an anthracycline to platinum-based chemotherapy is associated with a significant survival advantage. We are therefore conducting an ongoing phase I/II study combining drugs from these three classes. We report here the first phase using carboplatin at an area under the concentration-time curve of 7, doxorubicin 50 mg/m2, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 over 3 hours. The treatment was given on a 3-weekly cycle and granulocyte colony-stimulating factor was given if the nadir neutrophil count fell below 0.5 x 10(9)/L and was continued until recovery. Toxicity was assessed according to the Common Toxicity Criteria. All patients were required to have advanced ovarian cancer (stage IC to IV) but be ineligible for standard chemotherapy trials or to have advanced gynecologic malignancy, such as mixed mullerian tumor, fallopian tube carcinoma, coelomic carcinoma, or primary peritoneal carcinoma. To date, seven patients have been treated, and all were of performance status 0 to 2, 18 to 70 years old, with a life expectancy of > or = 3 months. Hematologic toxicity was significant, with all patients having grade 3/4 thrombocytopenia and six of seven grade 3/4 leukopenia. There was, however, only one grade 3/4 infection. Three patients have experienced fatigue, which in two cases was severe, and one patient had grade 3/4 stomatitis. Dose reduction was due to myelosuppression and was required in five patients. Five patients were evaluable for response, all of whom have obtained complete or partial response. There has been no clinical evidence of cardiotoxicity, but four patients had grade 1/2 cardiotoxicity as measured by left ventricular ejection fraction. We conclude that this combination is active and has acceptable but significant toxicity. It is only suitable for very fit patients, and we are currently assessing ways of reducing toxicity.

Antineoplastic Combined Chemotherapy Protocols↗