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Biomedical subjects

G J Rustin

Publications and source records attributed to G J Rustin.

At least 127 records · Page 7Linked to original sources
PubMed1988

Single agent activity of methotrexate in advanced non-seminomatous testicular germ cell tumours.

The single agent activity of methotrexate in non-seminomatous germ cell tumours (NSGCT), and thus the rationale for its inclusion in combination regimens, has never been documented clearly. We have therefore reviewed all patients with NSGCT treated in this hospital from 1967 to 1970. Seventeen patients were identified who had a rising HCG excretion and who were treated with methotrexate alone as first line chemotherapy. Nine patients (53%) obtained a partial remission and a further seven patients a reduction in HCG production that was less than one log. Methotrexate is an active agent in testicular germ cell tumours and should be of particular value in treating CNS disease where intrathecal treatment may be required.

Adolescent↗
PubMed1988

Single agent etoposide in gestational trophoblastic tumours. Experience at Charing Cross Hospital 1978-1987.

Two hundred and two patients with gestational trophoblastic tumours (GTT) were treated using single agent etoposide. Patients were divided into low, medium and high risk groups using a prognostic index. Initial chemotherapy commenced with etoposide in 101 patients and 94 were accessible. Partial response (PR), defined by a log fall in serum human chorionic gonadotrophin (hCG) concentration within 1 week, occurred in 63 patients (67%) and was more common among low (5/8; 63%) and medium risk (47/64; 73%) than high risk patients (11/22; 50%) although these differences were not significant (P greater than 0.05). No patient showed a sustained rise in hCG level after etoposide and 91 (97%) showed some decrease. Ninety-one (97%) of these patients remain alive and well with median follow-up of 63 months but 29 (31%) required more intensive combination therapy. Of three deaths, two were due to progressive disease and drug resistance. Among 101 patients who had received previous chemotherapy when etoposide was first administered, response to etoposide was accessible in 39. Of these, PR occurred in 18 (46%) and only one patient progressed after etoposide. With a median follow-up of 35 months, survival in this group is 92% (36/39). All deaths were due to progressive disease and drug resistance. Single agent etoposide is very active in GTT but should be used in combination chemotherapy for patients presenting with adverse prognostic factors.

Adult↗
PubMed1988

Treatment of advanced malignant melanoma with interferon alpha and etretinate.

The combination of recombinant human interferon alpha A 9 MU daily intramuscularly and etretinate 50 mg daily orally was given to 25 patients with progressive advanced, metastatic melanoma. The treatment was well tolerated. Partial responses were seen in three (12%) patients lasting from 2 to 8 months. A further partial response was seen in one of three patients when they were given vindesine and DTIC whilst they continued receiving interferon and etretinate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Bone disease in testicular and extragonadal germ cell tumours.

Of 297 patients with metastatic testicular and extragonadal germ cell tumours (GCT), bone involvement was detected clinically in 3% (7/251) of those at first presentation and in 9% (4/46) of relapsed cases. This difference was not statistically significant (95% confidence limits -2%; +14%). Concurrent systemic metastases, commonly involving lung (7/11 cases) and para-aortic lymph nodes (6/11), were present in all patients with bone disease. All affected patients had localized bone pain and lumbar spine was the most frequent site involved (9/11). Spinal cord compression occurred in two patients while a third developed progressive vertebral collapse after chemotherapy and required extensive surgical reconstruction. At median follow-up of 4 years, survival among patients presenting with bone disease (6/7) was similar to overall survival in the whole group (84%) and appeared better than in those with liver (18/26, 69%) or central nervous system (6/9) metastases at presentation. Back pain in metastatic germ cell tumours is often due to retroperitoneal lymphadenopathy but lumbar spine osseus metastases must be recognized early if severe potential complications, such as spinal cord compression, are to be avoided. In this series, bone metastases were not seen in the absence of widespread systemic disease suggesting all solitary bony lesions in GCT patients should be biopsied.

Adolescent↗
PubMed1988

Phase I-II study of carboplatin vincristine methotrexate and bleomycin (COMB) in carcinoma of the cervix.

Platinum based combination chemotherapy has been associated with a high response rate in patients with cervical carcinoma. To determine whether the toxicity could be reduced but the efficacy maintained carboplatin 200 mg m-2 was substituted for cisplatin in a regimen that was repeated two weekly and also contained vincristine, methotrexate and bleomycin. Twenty-four patients with squamous cell carcinoma of the cervix of whom 17 had relapsed following radiotherapy were studied. Only 5 of the 19 evaluable patients had a partial response (26%, 95 confidence limits 45.7-6.3%) compared to 30 of 43 (70%, 84-56%) who received a cisplatin combination in a previous study (P less than 0.01) (Rustin et al., 1987). Carboplatin as given in the COMB regimen appears less effective than cisplatin containing combinations for squamous cell carcinoma of the cervix.

Adult↗
PubMed1988

Safety of surveillance in the management of stage I anaplastic germ cell tumours of the testis.

A study was made of 46 patients with anaplastic germ cell tumours of the testis with no evidence of disease elsewhere as judged by computed tomography (CT) of thorax and abdomen, ultrasound and tumour marker measurements. A repeat CT 3 months after the first and clinical examination with chest X-ray and tumour marker measurements ensured that the 30.7% of patients who relapsed were detected promptly enough for them all to enter complete remission. Lymphography as part of the staging did not reduce the relapse rate. There was no difference between this group and a comparable group who underwent radiotherapy to para-aortic lymph nodes.

Biomarkers, Tumor↗
PubMed1987

Surgery, chemotherapy and whole abdominal radiotherapy in the management of advanced ovarian carcinoma.

A pilot study on 35 women was performed to determine the feasibility of giving whole abdominal radiotherapy after surgery and chemotherapy for Stage III and IV ovarian adenocarcinoma. The planned duration of therapy was only 6 months from diagnosis. Chemotherapy consisted of four courses of cis-platinum 100 mg/m2 alternating every 10-12 days with four courses of methotrexate 300 mg/m2 and cyclophosphamide 500 mg/m2 followed by folinic acid rescue. Twenty-nine of 35 (83%) patients were shown at second look surgery after chemotherapy to have residual tumour deposits no more than 2 cm in diameter. The usual radiotherapy dose was 2400 cGy in 20 fractions over approximately 4 to 5 weeks, with kidney shielding, and was generally well tolerated. Three patients failed to complete radiotherapy, two because of progressive disease and one because of persistent nausea and vomiting. During radiotherapy the white blood count fell below 2.0 X 10(9)/litre in seven patients (26%), and in eight patients (30%) the platelet count fell below 75 X 10(9)/litre. However, the white blood count nadir of 1.5 X 10(9)/litre was reached by 1300 cGy and the platelet nadir of 45 X 10(9)/litre was reached by 1400 cGy and both then levelled or recovered despite continuing radiotherapy. The median follow up since diagnosis is 26 months. Four of 12 patients with no tumour detected at second look operation have relapsed compared with 13 of 15 patients who had detectable tumour. Toxicity of this multi-modality therapy was acceptable.

Abdomen↗
PubMed1987

Treatment of patients with poor prognosis anaplastic germ cell tumours (AGCT) of the testis and other sites.

Between 1977 and 1986, 170 male patients with anaplastic germ cell tumours (AGCT) completed chemotherapy with POMB/ACE (platinum, vincristine (oncovin), methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide). By increasing the number of courses of POMB in 1979 we have been able to compensate for adverse prognostic factors. Since then each patient has received a minimum of three courses of POMB and 139 patients have completed therapy with an overall survival of 89%, and for those patients who had not received prior radiotherapy the survival is 92%. By increasing the number of courses of POMB, the initial serum concentrations of human chorionic gonadotrophin (hCG greater than 50,000 IU/I) and/or alpha-fetoprotein (AFP greater than 500 kU/l) have ceased to be poor prognostic variables. Neither stage at presentation nor the volume of metastatic disease is a major adverse prognostic variable using this chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Fertility after chemotherapy for male and female germ cell tumours.

Gonadal function was assessed in fifty-nine men and thirty-one women who had successfully completed chemotherapy with the POMB/ACE regimen for germ cell tumours. Seventeen (81%) of the twenty-one men who had not received paraaortic radiotherapy, whose original tumour bulk was less than 5 cm and whose duration of chemotherapy was less than 6 months, recovered spermatogenesis compared with twelve (32%) of thirty-eight patients who had either larger tumour masses or longer courses of chemotherapy, or both. All but one of the seventeen women in whom menstruation could have been expected to recur are now menstruating. This study suggests that the great majority of patients treated with POMB/ACE chemotherapy for germ cell tumours will recover fertility.

Adolescent↗
PubMed1987

Cisplatin, vincristine, methotrexate and bleomycin (POMB) as initial or palliative chemotherapy for carcinoma of the cervix.

Chemotherapy was given as initial therapy to 12 women with very advanced squamous cell carcinoma of the cervix and to 19 women with recurrent disease. They received a median of four courses of POMB which comprised vincristine 1.0 mg/m2 and methotrexate 300 mg/m2 followed by folinic acid rescue, bleomycin 30 mg as a 48-h infusion or intramuscular injection and cisplatin 100 mg/m2 as a 12-h infusion. Two of the 14 assessable patients with recurrent disease (14%) had a complete response with no disease found histologically in one, and seven (50%) had a partial response. Although the actuarial median survival of all 19 patients with recurrent disease was 8 months, five patients have remained free from tumour progression for a median of 17 months from start of chemotherapy. Six of the 10 assessable patients receiving initial chemotherapy (60%) had a complete response (confirmed histologically in two) and two (20%) had a partial response. Nine patients had additional treatment with radiotherapy and or surgery. Although only four of the patients remain disease-free at 61, 51, 7 and 4 months, all but two were initially FIGO stage IV. Although cisplatin-induced emesis is controllable and the side-effects of methotrexate can be avoided, the POMB regimen remains potentially toxic. The small number of patients with very advanced disease who are long-term survivors prompts us to study further the role of aggressive chemotherapy as the initial treatment of patients with visceral or nodal involvement from carcinoma of the cervix.

Adult↗
PubMed1987

Fertility after chemotherapy for ovarian germ cell tumours.

Gonadal function was assessed in 17 women who successfully completed chemotherapy with the POMB/ACE regimen (cisplatin, vincristine [Oncovin], methotrexate, bleomycin/actinomycin D, cyclophosphamide, etoposide) for ovarian germ cell tumours, and had a remaining ovary and uterus. A 20-year-old girl has not yet recovered menstruation 5 months off chemotherapy. All the remaining women whose mean age at start of chemotherapy was 21 (9-38) are now menstruating with a median time of recovery of 41/2 months after completion of chemotherapy. Five women have so far conceived after chemotherapy resulting in three full term normal deliveries of healthy infants, one termination of pregnancy, two miscarriages and one continuing pregnancy. Gonadal function does not appear to be permanently impaired in the majority of patients receiving POMB/ACE chemotherapy for ovarian germ cell tumours.

Adolescent↗
PubMed1986

Successful management of metastatic and primary germ cell tumors in the brain.

Nine men and one woman with brain metastases from nonseminomatous germ cell tumors have been treated between 1977 and 1984. All the men had lung metastases. Nine patients had elevated serum values of human chorionic gonadotrophin (HCG), the level was greater than 40,000 IU/l in seven. They were treated with sequential combination chemotherapy either POMB/ACE or EP/OMB in which the methotrexate was given at a dose of 1 g/m2 and intrathecal methotrexate was given during courses not containing intravenous methotrexate. Eight of ten patients are alive, off treatment with no evidence of active disease, of whom five have been in remission and off treatment for more than 18 months. Two patients with primary intracranial nonseminomatous germ cell tumors were treated in a similar fashion. One patient died from enlargement of differentiated teratoma; the other is alive 9+ months off treatment with no evidence of disease. These results, which are better than any previously reported, indicate that chemotherapy is the preferred treatment of primary or metastatic nonseminomatous germ cell tumors of the brain and that only rarely will these patients benefit from surgery or radiotherapy.

Adolescent↗
PubMed1986

Fertility in patients with gestational trophoblastic tumors treated with etoposide.

The effect of etoposide containing drug combinations on reproductive performance was studied in women successfully treated for gestational trophoblastic disease between 1977 and 1984. Of the 74 women who wished to get pregnant 57 (77.0%) succeeded in having at least one live birth while five (6.8%) have ongoing pregnancies. Of eight (19.8%) women who have not become pregnant two (2.7%) had previous infertility problems antedating the development of gestational trophoblastic disease. The miscarriage rate was 124/1000. There was only one case of foetal death and one congenital abnormality (microcephaly possibly associated with cytomegalovirus infection) among 79 live births and stillbirths. This study indicates that etoposide (VP16-213) as is currently used in this unit for the treatment of gestational trophoblastic tumour is unlikely to have any long-term effect on fertility in most women.

Adult↗