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Biomedical subjects

G J Rustin

Publications and source records attributed to G J Rustin.

At least 55 records · Page 3Linked to original sources
PubMed1997

FaFEC: a novel regimen for advanced ovarian cancer.

A palliative combination chemotherapy regimen (FaFEC) was developed for patients with relapsed epithelial ovarian cancer in particular patients relapsing after, or ineligible to enter, phase II trials, usually due to lack of evaluable disease. Forty-six patients were enrolled. Patients had received a mean of 2.3 previous drug regimens and nine (19%) had intestinal obstruction at the start of FaFEC. The majority of patients were inevaluable by WHO criteria so objective response data was obtained from serial serum CA125 evaluations. A serological response was demonstrated in 8/44 (18%). The responders included 6/27 women who had a prior relapse-free interval of less than 3 months, four who were resistant to platinum chemotherapy and three patients who had previously received paclitaxel. The major (WHO grade 3/4) toxicities included leucopenia (six patients), anemia (three patients), thrombocytopenia (two patients), nausea and vomiting (four patients) and severe infections (five patients). Following FaFEC the median time to failure was 0.48 years and the median survival was 0.66 years. FaFEC was effective in this group of very poor prognosis patients. The serological response rate of 18% is noteworthy considering the multiple prior treatments that patients had received and the short treatment free intervals. FaFEC may be useful second line therapy in epithelial ovarian cancer patients ineligible for phase II studies and should be considered for a randomized comparison with paclitaxel.

Journal Article↗
PubMed1997

Gestational trophoblastic disease with liver metastases: the Charing Cross experience.

OBJECTIVE: To define management options for women presenting with gestational trophoblastic disease (GTD) which had already metastasised to the liver. DESIGN: Retrospective analysis of case records between 1958 and 1994. SETTING: A national referral centre for trophoblastic disease. RESULTS: The database containing 1676 treated patients was reviewed and 46 patients with hepatic metastases were identified (2.7%). The median age was 32 years (range 19-52 years). The antecedent pregnancy to the GTD was normal in 65% (30/46), and the time interval between the antecedent pregnancy and presentation was longer than one year in 50% (22/44). Lung metastases were present in 43 patients (93%) and brain deposits in 15 patients (33%). Forty-five patients (98%) were high risk by WHO criteria. The five-year overall survival was 27%. The five-year survival of the subgroup of patients having both hepatic and cerebral metastases was 10%. There was no significant survival difference between the different chemotherapy regimens used in the study period (pre-1979 CHAMOCA: methotrexate, actinomycin D, cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine; 1979 onwards EMA/CO-EP: etoposide, methotrexate, adriamycin-D/ cyclophosphamide, vincristine-etoposide and cis-platinum). Multivariate analysis revealed that a prognostic score > 12 was significant (Hazard ratio 5.4, 95% CI 0.7-41.9; P = 0.04). CONCLUSIONS: The outcome for women presenting with hepatic metastases from GTD is poor with an even worse prognosis if cerebral metastases are also present. Alternative therapeutic measures, such as high dose therapy or new drugs, should be explored in these women.

Adult↗
PubMed1997

Phase II trial of oral altretamine for relapsed ovarian carcinoma: evaluation of defining response by serum CA125.

PURPOSE: A phase II study was performed of oral altretamine in 71 patients with ovarian carcinoma who entered clinical complete remission with CA125 levels less than 35 U/mL after initial or second-line chemotherapy, and relapsed more than 6 months later. Response was compared between standard and CA125-based criteria. PATIENTS AND METHODS: Altretamine 260 mg/m2 was given in divided doses daily for 14 days per month. Response was evaluated according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 45 of 66 eligible patients. Response was assessed according to precise CA125 criteria in 51 patients based on either a confirmed > or = 50% or > or = 75% decrease in CA125 levels. RESULTS: A combination of domperidone, dexamethasona, and chlorpromazine at night controlled toxicity in most patients, which was mainly nausea (National Cancer Institute criteria grade 2 or 3 in 27), vomiting (grade 2 or 3 in 19, grade 4 in one), and tiredness (grade 2 or 3 in 15). Responses (complete plus partial) were seen in 18 (40%; 95% confidence interval [CI], 25.4% to 54.6%) of those evaluated according to EORTC criteria and in 20 (39%; 95% CI, 25.5% to 52.9%) of those evaluated according to CA125 level. The overall response rate was 26 of 57 (45.6%) and was related to treatment-free interval: 6 to 12 months, 35%; 12 to 24 months, 52%; and greater than 24 months, 67%. The medium duration of response was 8 months. CONCLUSION: Oral altretamine is a useful agent in patients-who relapse after previously responsive ovarian cancer. Response evaluation by a strict CA125 definition gave a similar estimate of the efficacy of altretamine as EORTC criteria.

Administration, Oral↗
PubMed1997

Surveillance policy for stage I ovarian germ cell tumors.

PURPOSE: Surveillance for stage I male germ cell tumors (GCT) is well established as a standard practice; however, such a policy has not been evaluated for women with equivalent tumors. This study was designed to evaluate the management of grade II or higher stage Ia tumors by close surveillance to minimize treatment, while reserving chemotherapy for patients with residual or recurrent disease. PATIENTS AND METHODS: Between 1973 and 1995, 24 patients with malignant stage Ia ovarian GCT were enrolled onto a surveillance program. The group consisted of nine patients with dysgerminoma, nine with pure immature teratoma, and six with endodermal sinus tumor (with or without immature teratoma). Treatment consisted of surgical resection without adjuvant chemotherapy, followed by a surveillance program of clinical, serologic, and radiologic review, and included a second-look procedure for patients enrolled after 1982. RESULTS: All but one patient are alive and in remission after a median follow-up of 6.8 years. The 5-year overall survival is 95%, and the 5-year disease-free survival is 68%. Eight patients have required chemotherapy for recurrent disease or second primary ovarian GCT. This includes three patients with grade II immature teratoma and three patients with dysgerminoma, and a further two women with dysgerminoma who developed contralateral (presumed second primary) dysgerminoma 4.5 and 5.2 years after their first tumor. All but one, who died of a pulmonary embolus, have been successfully salvaged with chemotherapy. CONCLUSION: Our experience emphasizes that patients with true stage Ia ovarian GCT are adequately managed by surgical resection followed by careful clinical, radiologic, and serologic surveillance. These patients do not require adjuvant chemotherapy or radiotherapy, thus avoiding the potential complications of secondary leukemia and infertility.

Antineoplastic Agents↗
PubMed1997

EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients.

PURPOSE: To evaluate the results of etoposide, methotrexate, and dactinomycin alternating with cyclophosphamide and vincristine (EMA/CO) chemotherapy in women with high-risk gestational trophoblastic tumors (GTT) and to document the middle- and long-term toxicity of the regimen. PATIENTS AND METHODS: A total of 272 consecutive women with high-risk GTT, including 121 previously treated patients, were treated with weekly EMA/CO. The median follow-up duration is 4.5 years (range, 1 to 16). RESULTS: The cumulative 5-year survival rate is 86.2% (95% confidence interval, 81.9% to 90.5%). No deaths from GTT have occurred later than 2 years after the end [corrected] of EMA/CO. In a multivariate model, adverse prognostic factors were the presence of liver metastases (P < .0001), interval from antecedent pregnancy (P < .0001), brain metastases (P = .0008), and term delivery of antecedent pregnancy (P = .045). There were 11 (4%) early deaths, while 213 patients (78%) achieved a complete remission. Forty-seven (17%) developed drug resistance to EMA/CO, of whom 33 (70%) were salvaged by further cisplatin-based chemotherapy and surgery. Two women developed acute myeloid leukemia, two cervical malignancy, and one gastric adenocarcinoma after EMA/CO. More than half (56%) of the women who had fertility-conserving surgery and who have been in remission at least 2 years have become pregnant since the completion of EMA/CO, with 112 live births, including three infants with congenital abnormalities. CONCLUSION: EMA/CO is an effective and well-tolerated regimen for high-risk GTT. More than half of the women will retain their fertility; however, there is a small but significant risk of second malignancy.

Adolescent↗
PubMed1996

Metastatic cerebral choriocarcinoma coexistent with a viable pregnancy.

Gestational choriocarcinoma associated with a viable pregnancy is extremely rare, and such choriocarcinoma with metastases presenting during the pregnancy is even more exceptional. Metastases from this tumor may present in a variety of ways depending on the site of the metastatic lesion, and can be fatal before choriocarcinoma is even suspected. We describe a 32-year-old primigravida presenting at 31 weeks gestation with a grand mal seizure due to cerebral metastases secondary to gestational choriocarcinoma who was subsequently successfully treated with chemotherapy. To our knowledge this is the first reported case of choriocarcinoma presenting with signs due to cerebral metastases during pregnancy where both the mother and child survived. This paper emphasizes the need to consider metastatic choriocarcinoma in any gravid female who presents with unusual neurological signs because of the life-threatening nature of this potentially curable disease.

Adult↗
PubMed1996

Chemotherapy for ovarian germ cell tumours.

59 patients were treated for newly diagnosed metastatic ovarian germ cell tumours with POMB/ACE chemotherapy (which contains cisplatinum, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide). The median follow-up was 7.7 years. The 3 year survival is 87.8% (95% confidence interval 76.9-93.9%) and no relapses occurred more than 3 years after treatment. 4 (7%) patients had primary drug resistance to POMB/ACE and 4 (7%) have relapsed. One patient in complete remission developed secondary acute myeloid leukaemia after receiving a total of 1.3 g/m2 etoposide. 6 of 12 (50%) patients referred at relapse were salvaged by POMB/ACE. 14 of 33 (42%) women (> 18 years old) have had successful pregnancies after fertility conserving surgery and chemotherapy with no congenital abnormalities reported. The POMB/ACE regimen is as efficacious as other published regimens for ovarian germ cell tumours (OGCT) and balances a low incidence of life-threatening toxicity with a high success rate.

Adolescent↗
PubMed1996

Attempted preservation of one gonad in patients with bilateral germ cell tumours.

Almost all patients with early stage testicular or ovarian germ cell tumours can now expect to be cured of their disease. The preservation of fertility and sex hormone production after treatment are of importance in these predominantly young adults, especially in the uncommon cases of bilateral tumours. We present the case reports of a woman with bilateral dysgerminoma and a man with bilateral testicular seminoma, who were managed by organ-sparing surgery of the least affected gonad followed by chemotherapy. Both patients regained fertility, but a further germ tumour has developed in the man's remaining testicle. The merits and potential pitfalls of this approach are discussed.

Adult↗
PubMed1996

Phase I trial of elactocin.

Elactocin is a novel anti-tumour antibiotic which has potent activity in vitro against a range of tumours. This phase I trial of elactocin identified the dose-limiting toxicity as profound anorexia and malaise. The schedules used included 1 h infusion 3 weekly, 24 h infusion 3 weekly, 1 h infusion daily x 5 (3 weekly), 1 h infusion weekly and finally continuous 5 day intravenous infusion. On all these schedules dose-limiting toxicity was the same and as no partial or complete responses were identified, we do not recommend that further trials of elactocin are performed.

Anorexia↗
PubMed1996

Trial of isotretinoin and calcitriol monitored by CA 125 in patients with ovarian cancer.

Twenty-two asymptomatic women with rising CA 125 levels after chemotherapy for ovarian cancer were entered into a trial of isotretinoin combined with calcitriol. Tumours were evaluated according to precise criteria based on serial CA 125 levels and by comparing regression slopes of CA 125 before and during therapy. There was no evidence based on CA 125 of any responses or significant change in tumour growth rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Defining progression of ovarian carcinoma during follow-up according to CA 125: a North Thames Ovary Group Study.

BACKGROUND: Many studies have shown that CA 125 levels frequently rise prior to clinical evidence of progression of ovarian cancer. For clinical trials an accepted definition of progression according to CA 125 is required. We therefore determined what change in CA 125 level was the most accurate predictor of relapse in patients on follow up after therapy for ovarian cancer. PATIENTS AND METHODS: Serial CA 125 levels were studied from 255 patients entering the North Thames Ovary Trial of 5 versus 8 courses of chemotherapy. An initial analysis was made 2 months after closure of the trial, a more detailed analysis was made after 81 confirmed relapses among evaluable patients and a final analysis was made one year later with longer follow-up. RESULTS: On the basis of the results from the interim analyses and the cut-off level of 22-35 U/ml used by different laboratories, 30 U/ml was chosen as the upper limit of normal. In the final analysis a doubling of CA 125 from the upper limit of normal was defined as progression. Using this method sensitivity was 85.9%, specificity 91.3%, positive predictive value 94.8%, and negative predictive value was 77.8%. Insisting on a confirmatory elevated CA 125 level reduced the false positive rate to < 2% with a sensitivity of 83.9%. The median lead-time prior to clinical progression was 63 days. CONCLUSION: A confirmed rise of serum CA 125 level to more than twice the upper limit of normal during follow up after first line chemotherapy accurately predicts tumour relapse.

CA-125 Antigen↗
PubMed1996

Circulating tumor markers in gynecological tumors.

The correct use of tumor markers in patients with gynecological cancers can make an impact on management of the disease. Their value in screening for ovarian cancer cannot be recommended outside trials. Increased levels of various markers give prognostic information that could alter therapy for patients with early ovarian or cervical carcinoma. Their main value is in monitoring the response to therapy and confirming relapse, for which they may be superior to scans.

Antigens, Neoplasm↗
PubMed1996

Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors.

PURPOSE: No increase in second tumor incidence was found in a previous analysis of women treated with chemotherapy for gestational trophoblastic tumors (GTT). More patient years at risk enabled a further analysis of the risk of second tumors to be performed in the 1,377 women treated in this until up to 1990. PATIENTS AND METHODS: Health questionnaires were returned on 93.3% of patients who successfully completed chemotherapy and were living in the United Kingdom. The remainder were flagged for death or developing further cancers by the Office of Population Census and Surveys and by the Thames Cancer Registry. Incidence density analysis was performed based on 15,279 person-years of observation available. Standardized incidence ratio (SIR) was used to estimate the relative risk (RR) of second tumors associated with the treatment. To calculate the expected number, the actual incidence rates observed by the Thames Cancer Registry during the same calendar period of observation were used. RESULTS: An overall 50% excess of risk (RR = 1.5; 95% confidence interval [CI], 1.1 to 2.1; P < .011) was observed: there were 37 second tumors, when 24.5 were expected. For specific second tumors, the risk was significantly increased for myeloid leukemia (RR = 16.6; 95% CI, 5.4 to 38.9), colon (RR = 4.6; 95% CI, 1.5 to 10.7), and breast cancer when the survival exceeded 25 years (RR = 5.8; 95% CI, 1.2 to 16.9). The risk was not significantly increased among the 554 women receiving single-agent therapy (RR = 1.3; 95% CI, 0.6 to 2.1). Leukemias only developed in patients receiving etoposide plus other cytotoxic drugs. CONCLUSION: This study suggests that there is a slight increased risk of second tumors after sequential or combination chemotherapy for GTT. This has become apparent since the introduction of etoposide and longer follow-up.

Adolescent↗
PubMed1996

Defining response of ovarian carcinoma to initial chemotherapy according to serum CA 125.

PURPOSE: To produce definitions based on serial CA 125 levels to measure response of ovarian carcinoma in patients receiving first-line chemotherapy. PATIENTS AND METHODS: Definitions were derived from analysis of 277 patients in North Thames Ovary Trial 3. Patient data were then incorporated into a computer program and tested against 254 patients in North Thames Ovary Trial 4 and 458 patients in Gynecologic Oncology Group (GOG) protocol 97. For optimum detection of response, three response definitions have been combined into a computer program. The precise definitions use mathematic logic and take account of factors such as intervening samples. Response to a specific treatment has occurred if after two samples there has been a 50% decrease, confirmed by a fourth sample (50% response), or a serial decrease over three samples of greater than 75% (75% response). The final sample has to be at least 28 days after the previous sample. RESULTS: Six hundred twenty of 989 patients were considered assessable for response according to CA 125 level. Only two patients (0.3%) had a CA 125 response at the time of clinical progression. The CA 125 response rate was 62% and 54% in the North Thames trials. In the GOG trial, it was 66% in all 317 patients assessable for CA 125 and 67% in 221 patients whose CA 125 level was not measurable according to GOG criteria, compared with a GOG-defined response rate of 62%. The sensitivity for detecting GOG-defined response was at least 68%. CONCLUSION: Definitions based on a 50% or 75% decrease of CA 125 levels have been shown reliably to define partial response of ovarian cancer in patients receiving first-line chemotherapy. These definitions should be used in addition to or instead of standard response criteria.

Antineoplastic Agents↗
PubMed1996

Patient compliance with prolonged oral altretamine treatment in relapsed ovarian cancer.

Using an 'intelligent' tablet bottle which, unknown to the patient, electronically records the times of opening, we have assessed the compliance of patients with prescribed oral altretamine for ovarian cancer. During the periods of compliance monitoring the physical and mental state of the patients was also monitored by means of self-assessed diary cards. 11 patients were assessed over 21 monitoring periods, each of 14 days, representing a total of 294 days. The Overall Compliance (OC), which we define as the number of bottle openings in a monitoring period as a percentage of that number expected on the assumption of perfect compliance, had a mean (SD) of 97.4 (6.9)% over the 21 periods. The OC was not related to any of the diary card measures, or to the cycle number (range 1-5) of the treatment. The high level of compliance is encouraging and is in line with our previous reports in patients with lymphoma and with small cell lung cancer.

Administration, Oral↗
PubMed1996

Placental site trophoblastic tumor: molecular analysis and clinical experience.

Placental site trophoblastic tumor is a very rare variant of gestational trophoblastic disease which differs histologically and immunocytochemically from gestational choriocarcinoma. The English language literature includes only 74 reported cases. Seventeen patients have been managed at Charing Cross Hospital with this diagnosis. The median follow-up is 4.6 years, and the 5-year overall survival is 80% (95% confidence interval, 55-93%). Multivariate regression analysis identified an interval of >2 years since the preceding pregnancy as an independent adverse prognostic factor. Genotypic analysis by PCR allelotyping has confirmed the gestational origin of all 11 tumors successfully studied. More detailed molecular analysis has identified the causative pregnancy for eight tumors. Five were diploid biparental tumors following term pregnancies, and three were androgenetic tumors following monospermic complete hydatidiform moles.

Adult↗
PubMed1995

Phase II trials of rhizoxin in advanced ovarian, colorectal and renal cancer.

Rhizoxin is a tubulin-binding anti-neoplastic agent which is active in a range of murine tumour models. The recommended schedule, of intravenous (i.v.) bolus administration at a dose of 2 mg m-2 every 3 weeks, has been assessed in three phase II trials of ovarian, renal and colorectal cancer. In general terms the drug was fairly well tolerated, but the response rate was disappointing: 0/18, colorectal cancer; 0/18, renal cancer; 1 partial response (PR)/17, ovarian cancer.

Adult↗