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Biomedical subjects

M J Peckham

Publications and source records attributed to M J Peckham.

At least 73 records · Page 4Linked to original sources
PubMed1983

Chemotherapy and radiotherapy for advanced testicular non-seminoma. I. The influence of sequence and timing of drugs and radiation on the appearance of normal tissue damage.

Acute and delayed normal tissue damage has been investigated in 63 advanced stage testicular non-seminoma patients receiving elective involved-field irradiation after chemotherapy and in 53 patients who had chemotherapy given for relapse after prior irradiation. The risk of death from complications due to chemotherapy was 0% and 9.4% (p less than 0.025) in the two groups respectively. Gastro-intestinal damage and/or subcutaneous fibrosis was present in 12.6% and 24.5% of patients respectively, although only three patients have serious persisting disability. In patients receiving 35-45 Gy to the retroperitoneum the incidence of normal tissue damage was 0% and 25% (p less than 0.001), respectively. In addition to the sequence in which chemotherapy and radiotherapy was delivered, the time interval between completion of radiotherapy and start of chemotherapy was important with 6/6 patients receiving drugs within 2 months of irradiation developing fibrosis. Abdominal surgery appeared not to influence the risk of damage. Of nine patients receiving drugs after infradiaphragmatic and supra-diaphragmatic irradiation two died of neutropenic sepsis.

Antineoplastic Agents↗
PubMed1983

The response to chemotherapy of a variety of human tumour xenografts.

The results of a series of projects on the cytotoxic drug response of human tumour xenografts are compared. All were performed in one laboratory, using conventional CBA mice that were usually immunosuppressed by thymectomy, cytosine arabinoside treatment, and whole-body irradiation. Results on human tumours arising in 9 anatomical sites are included, with the main emphasis on colo-rectal, pancreas, breast, lung and testis carcinomas, also melanomas. Growth acceleration during successive passage of most of these tumour types was observed. When therapeutic response was measured by a growth-delay method there were wide differences in response to chemotherapy. Testicular teratomas and small-cell lung tumours responded well; breast tumours showed modest response; melanomas, colo-rectal tumours and non-small-cell lung tumours responded poorly. Studies of clonogenic cell survival were made in 11 xenografted tumour lines. They confirmed the range of responsiveness and tendency towards individuality of the growth delay data. Cell survival in most cases was exponentially related to drug dose. This compilation of a large amount of experimental data supports the belief that human tumour xenografts broadly maintain the level of chemotherapeutic responsiveness of the source tumours in man.

Animals↗
PubMed1983

The treatment of metastatic germ-cell testicular tumours with bleomycin, etoposide and cis-platin (BEP).

Between July 1979 and December 1981, 43 patients with metastatic germ-cell tumours (36 testicular non-seminomas and 7 testicular seminomas) were treated with 2-6 cycles of bleomycin, etoposide and cis-platin (BEP). Forty (93%) are alive, 37 (86%) with no evidence of disease. Of 36 men with testicular non-seminoma 30 (83.3%) are alive and disease-free at 8-38 months (median 17.0 months). In the latter group 25/28 (89.3%) who had had no prior irradiation are alive and disease-free. Fourteen non-seminoma patients had small volume metastases and 13 are in complete remission, as are 12/14 patients with bulky disease. All 7 patients with advanced seminoma are alive and disease-free. It is concluded that BEP is a well tolerated and effective first line treatment for patients with metastatic germ-cell tumours.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Occult germ-cell testicular tumours.

Eighteen men presenting with metastatic germ-cell malignancy in whom no primary tumour could be palpated in either testis are described. All patients had both testes in the scrotal sac and none had a history of maldescent. All had abdominal node involvement, in most cases associated with metastases at other sites. Ten men presented with Stage 4 disease, five with Stage 3 and three with Stage 2. The most common histological sub-type associated with an occult primary testicular tumour was trophoblastic malignant teratoma (9/18 patients). Abdominal pain (12 patients) and systemic symptoms (10 patients) were common presenting features. There was a history of testicular atrophy in eight patients and seven had experienced episodes of transient testicular pain up to 18 months before presentation. In three of four patients in whom the testis was examined histologically following a history of atrophy and/or pain, there was evidence of a primary tumour, manifest as spontaneous tumour regression (one), differentiation (one) or a small micro-primary trophoblastic teratoma (one). In a fifth patient an ultrasonic scan showed a 1-cm echogenic mass in an atrophic testis. In 10 patients the diagnosis of germ-cell malignancy was established by laparotomy. Obstructive uropathy was present in six patients, associated with haematuria in four patients.

Humans↗
PubMed1983

Chemotherapy of primary (in situ) testicular tumours: response in advanced metastatic disease.

Five patients in whom primary testicular tumours were left in situ during chemotherapy for extensive metastatic disease are described. In four patients, the response of the primary and secondary tumour was comparable. In the fifth a small tumour in the testis became palpable during chemotherapy at the same time as metastases, and regressed on treatment. One possible explanation for the latter observation is protection from chemotherapy of a small, possibly partly intratubular primary, by the blood-testis barrier.

Abdomen↗
PubMed1983

Orchiectomy alone for Stage I testicular non-seminoma. A progress report on the Royal Marsden Hospital study.

Eighty-four patients with clinical Stage I non-seminomatous germ-cell testicular tumours were entered into a prospective study after orchiectomy to evaluate a policy of close surveillance without lymph node irradiation or node dissection; 16 (19%) have manifested evidence of metastatic disease and received chemotherapy. All patients in the study are alive, 3 of the 16 relapsing patients are receiving chemotherapy and the 13 who have completed it are in complete remission at 4 to 43 months (mean 21). Relapses were diagnosed at 2 to 8 months (mean 5.3 months) after orchiectomy and were not invariably associated with elevated serum markers. The relapse rate was significantly higher for malignant teratoma undifferentiated (MTU) primary tumours than malignant teratoma intermediate (MTI) (40.7 and 6.8% respectively) and preliminary data suggest that the association of MTU with vascular invasion places the patient at high risk of relapse. Pre-orchiectomy serum marker status was not a significant prognostic factor. Despite sub-optimal surgical management in 11/84 patients no example of scrotal recurrence has been encountered. It is concluded that a rigorously monitored policy of close surveillance after orchiectomy is a feasible and successful method of management in Stage I testicular non-seminoma. Further experience should allow patients requiring immediate post-orchiectomy chemotherapy to be identified.

Castration↗
PubMed1983

Semen analysis in testicular cancer and Hodgkin's disease: pre- and post-treatment findings and implications for cryopreservation.

Over a 7-year period, seminal analysis has been performed on 208 patients with testicular tumours, after orchiectomy, but before any other treatment. Only 22% of 54 patients with seminomas, and 29% of 154 patients with teratomas or mixed tumours, had sperm counts exceeding 10 million per ml. Very low sperm counts were observed in some patients who had previously fathered children. Post-treatment sperm counts were done in 117 patients, 80 of whom had received multiple drug chemotherapy: 42 of these men had pre- and post-treatment sperm counts. Overall, 24% of men receiving chemotherapy recovered sperm counts greater than 10 million per ml up to 3 years after therapy. Surprisingly, such recovery was seen in 35% of 23 men with initially poor sperm counts, but in only 26% of 19 with good initial counts. Only 27% of 49 patients with Hodgkin's disease had initial sperm counts of more than 10 million per ml; after chemotherapy only 1 of 29 patients recovered to this level. Only one quarter of these young men had semen which was adequate for cryopreservation. Artificial insemination with semen preserved in liquid nitrogen has been performed in 15 couples: 2 normal babies have been produced and a third pregnancy is progressing normally.

Dysgerminoma↗
PubMed1982

The management of metastatic seminoma testis.

Clinical details of 85 men presenting with previously untreated metastatic seminoma are presented. In Stage II disease relapse rate was related to the size of metastases. In IIA (32 patients) the relapse rate was 9.4%; IIB (11 patients), 18.2%; and IIC (23 patients), 39.1%. The continuous disease-free survival rate was significantly worse for IIC than IIA and IIB patients (P = 0.023). No instance of first relapse in supradiaphragmatic nodes was observed in 13 men with Stage II disease treated with irradiation limited to infradiaphragmatic nodes. In relapsing Stage IIC patients, extralymphatic metastasis was as frequent as abdominal relapse. On the basis of these observations, together with preliminary data in nine men receiving Cis-platinum-containing chemotherapy, all of whom are in complete remission, it is proposed that patients with Stage IIA and IIB disease should receive infradiaphragmatic irradiation with chemotherapy deferred until relapse. Stage IIC patients should receive chemotherapy initially, followed by irradiation. In Stage III and IV disease chemotherapy should be initial therapy with radiotherapy for bulky disease on an individualised basis. Moderate elevation of blood B-HCG levels is not inconsistent with a diagnosis of pure seminoma and does not appear to influence adversely the outcome of radiotherapy.

Antineoplastic Agents↗
PubMed1982

Orchidectomy alone in testicular stage I non-seminomatous germ-cell tumours.

53 patients with clinical stage I non-seminomatous germ-cell testicular tumours were entered into a prospective study to receive no treatment other than orchidectomy until unequivocal clinical evidence of metastases was established. Of this group, 9 men (17%) have relapsed, 8 within six months of orchidectomy. All 9 are alive and disease-free after chemotherapy. The relapse rate was higher in patients with malignant teratoma undifferentiated (embryonal carcinoma) primary tumours than in those with malignant teratoma intermediate (teratocarcinoma); 42.8 and 3.4%, respectively. The results were compared with those from 157 men treated by orchidectomy and radiotherapy for stage I disease. In this group, 49 patients (25.8%) relapsed and 85% of relapses occurred within one year of orchidectomy. The tempo relapse was identical for embryonal carcinoma and teratocarcinoma. Of 32 patients in whom serum markers were measured before orchidectomy, 24 (75%) had raised levels of alphafetoprotein and/or beta human chorionic gonadotropin. These preliminary results imply that routine lymphadenectomy or lymph node irradiation in clinical state I testicular non-seminoma may be unjustifiable.

Dysgerminoma↗
PubMed1982

Etoposide as a single agent in relapsed advanced lymphomas. A phase II study.

Twenty-three patients with relapsed lymphomas resistant to standard chemotherapy, 13 with Hodgkin's disease and 10 with non-Hodgkin's lymphomas, were treated with etoposide 120 mg/m2 i.v. daily for 5 days or orally for 7-10 days, repeated 3-weekly. This is a higher dose than has been used previously to treat these tumours. Objective responses were seen in eight of 13 (61%) patients with Hodgkin's disease (three CR, five PR) and in three of 10 (30%) patients with non-Hodgkin's lymphomas (three PR). The response rates for Hodgkin's disease are higher than those previously reported and are probably due to the greater dose of drug than has been previously employed. The dose-limiting toxicity was haematological, with gastro-intestinal toxicity occurring in the minority of patients only. It is concluded that etoposide has significant activity particularly in Hodgkin's disease. Its use in drug combinations should now be assessed.

Adult↗
PubMed1982

Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II.

cis-Diammine-1,1-cyclobutane dicarboxylate platinum II (CBDCA, JM8), an analogue of cisplatin showing reduced toxicity in preclinical studies, was evaluated in 60 patients. Doses were given initially every 3 weeks and escalated from 20 to 520 mg/m2. Following this, doses were given every 4 weeks and escalated from 300 to 500 mg/m2. The dose-limiting toxicity, thrombocytopoenia, occurred in four-fifths of patients treated at 520 mg/m2, with the nadir occurring 3 weeks after treatment. Leucopoenia and anaemia also occurred but were less severe. Vomiting occurred in all patients receiving over 120 mg/m2 but seldom persisted beyond 24 h. Serial measurements of 51Cr-EDTA clearances, urinary N-acetylglucosaminidase, urinary leucine aminopeptidase, and beta 2-microglobulin did not reveal significant evidence of nephrotoxicity. Detriment to the audiogram has not been seen in the first 13 patients studied. Pharmacological studies showed that most of the dose of platinum was excreted in the urine, and that impairment of renal function may be associated with drug retention and an increased risk of myelosuppression. The previous therapy and age of the patient also affected the tolerance of the drug. Clinical responses were seen in patients with ovarian carcinoma receiving greater than 120 mg/m2. A further dose escalation was performed on a 4-week schedule in patients under 65 with good renal function. The maximum dose it was possible to administer repeatedly without incurring myelosuppression was in the range 400-500 mg/m2. JM8 is not significantly nephrotoxic and is less emetic than cisplatin. It has antitumour activity in man and deserves wider evaluation, along with the other analogues under study in various centres, as an alternative to cisplatin.

Adult↗
PubMed1982

Five years' experience with ChlVPP: effective low-toxicity combination chemotherapy for Hodgkin's disease.

Since 1975, 191 patients with Hodgkin's disease have been treated with a combination of chlorambucil, vinblastine, procarbazine and prednisolone (ChlVPP). Complete remission rates were 73% for previously untreated patients, 91% for patients previously treated with radiotherapy and 55% for patients previously treated with chemotherapy. In 59 patients with advanced disease who received no other treatment, a 5-year survival rate of 66% was comparable with that achieved by more toxic mustine-containing combinations. ChlVPP has few side effects, is easily given to outpatients, and can be combined with elective radiotherapy in selected patients.

Adolescent↗
PubMed1982

Experimental combination and single-agent chemotherapy in human lung-tumour xenografts.

A series of human bronchial-carcinoma xenografts (3 small-cell anaplastic, 2 large-cell anaplastic and 3 adenocarcinomas) established in immune-suppressed mice were treated with combination chemotherapy based on clinical regimes. Xenograft response was assessed by the in situ endpoint of growth delay in s.c. tumours. Dose-response relationships of 3 triple-drug combinations and their component agents were explored, allowing the relative contributions of single agents in each combination to be assessed. The results demonstrate that the effects produced in the xenografts were generally consistent with clinical experience. Procarbazine, cyclophosphamide and CCNU stood out as the most effective drugs in small cell carcinoma, but were ineffective in the other histological types. These was some evidence for individuality of therapeutic response among the grafts, supporting the case for incorporating panels of histologically similar xenografts into primary drug-screening programmes to complement existing syngeneic rodent tumour systems.

Adenocarcinoma↗
PubMed1982

Prognostic factors in clinical stage I non-seminomatous germ-cell tumours of the testis.

Prognostic factors have been studied in 59 men with clinical Stage I non-seminomatous germ-cell tumours of the testis (NSGCTT) seen at the Royal Marsden Hospital between 1973 and 1978. Fourteen of the patients relapsed, and 45 have remained continuously disease-free. Two factors were identified which showed a significant correlation with relapse following radiotherapy: local extent of the primary tumour, and rate of decline of serum alpha-foetoprotein (AFP) and beta-human chorionic gonadotrophin (hCG) levels following orchidectomy. High serum marker levels at the time of referral after orchidectomy were not prognostically significant per se. The presence of tissue-associated hCG in the primary tumour was not prognostically significant. The results were compared with histology and pathological stage of the primary tumour in patients presenting with lung metastases but no clinical evidence of lymph-node disease. Embryonal carcinoma was more commonly associated with a locally invasive primary tumour and with extralymphatic spread than was teratocarcinoma.

Adolescent↗