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Biomedical subjects

J H Scarffe

Publications and source records attributed to J H Scarffe.

At least 91 records · Page 5Linked to original sources
PubMed1987

A randomized trial of two types of adjuvant chemotherapy in radiotherapy-treated patients with clinical stages I and II high-grade non-Hodgkin's lymphoma.

This paper reports the 8-year results of comparing the use of two types of adjuvant chemotherapy following involved field radiotherapy for clinical stages I and II high-grade non-Hodgkin's lymphoma. Twenty-four patients received 6 weeks of VAP plus 2 years of oral maintenance chemotherapy, and 30 had six cycles of CMOPP. Four patients were not in complete remission at completion of i.v. chemotherapy (CR rate 91%). Ten patients (18.5%) have relapsed (VAP/M = 5; CMOPP = 5), with only two of these remaining alive, both of them being disease free. There have been three deaths from intercurrent causes, one from malignant melanoma and the other two from myocardial infarction. The relapse-free survivals at 2, 5 and 8 years were 80%, 76% & 76% respectively. The overall survivals at the same time points were 86%, 72% & 68%. There were no significant differences in either relapse-free or overall survival for either of the two treatment groups. The shorter period of weekly intravenous chemotherapy (VAP/M) was better tolerated than 36 weeks of CMOPP, and the former appears to produce equivalent results.

Adolescent↗
PubMed1987

Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer.

Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rhG-CSF) at the following dose levels: 1 microgram, 5 micrograms, 10 micrograms, 20 micrograms and 40 micrograms kg-1 day-1 for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neutrophils increased rapidly to a maximum of 100 x 10(9) l-1 at 10 micrograms kg-1 day-1. The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the phase II part of the study the patients were treated by a combination of intravenous adriamycin 50 mg m-2, ifosfamide 5 g m-2 by i.v. infusion with mesna 8 g m-2 on day 1, and etoposide 120 mg m-2 on days 1, 2 and 3 also intravenously. The chemotherapy regime was repeated every 3 weeks. RhG-CSF was given to each patient for 14 days on alternate cycles of chemotherapy and reduced the period of absolute neutropenia considerably (median of 80%), with a return to normal, or above normal, neutrophil counts within 2 weeks after day 1 of chemotherapy. Six severe infective episodes were observed during the cycles of chemotherapy which did not include rhG-CSF, while no infective episodes occurred when patients were treated with rhG-CSF. These results demonstrate the utility of rhG-CSF in restoring functional neutrophils to patients undergoing intensive chemotherapy.

Aged↗
PubMed1987

Phase I clinical trial of methylene dimethane sulfonate.

Methylene dimethane sulfonate is the first member of the homologous series of straight-chain diol sulfonates. It was selected for phase I testing because of high activity in the rat Yoshida sarcoma system and a possible novel site of alkylation due to its small molecular size. Methylene dimethane sulfonate was administered as a rapid iv bolus infusion to 39 patients at doses ranging from 14 to 225 mg/m2. Nausea and vomiting were not severe but total alopecia occurred in the majority of patients at doses greater than 100 mg/m2. The dose-limiting toxic effect was thrombocytopenia, which was cumulative with lower, more prolonged nadirs following successive courses. The median time to platelet count nadir was 21 days, with recovery by 35 days. A minor response was seen in one patient with an adenocarcinoma of the lung. The recommended dose for phase II studies is 125 mg/m2 for patients who have received prior chemotherapy and 150 mg/m2 for those who have not, in an every 35-day schedule.

Adult↗
PubMed1987

Phase II trial of rDNA alfa 2b interferon in patients with malignant carcinoid tumor.

Fourteen patients with malignant carcinoid tumors were treated with rDNA alfa 2b interferon by sc injection three times per week. Treatment was started at a dose of 2 milliunits/m2, with escalations to 3, 5, 7, and 10 milliunits/m2 at 2-week intervals depending on toxicity. No objective tumor regressions were seen, but five of 14 patients (36%) had 50% reduction in 24-hour 5-hydroxyindoleacetic acid excretion and six of nine (67%) with carcinoid syndrome had a good symptomatic response. Biochemical responses occurred during the first 8 weeks of treatment, and escalation of the dose of interferon did not increase the response rate. The rDNA alfa 2b interferon has activity in patients with the carcinoid syndrome and should be used at a low dose (2-3 milliunits/m2) until symptoms recur.

Adult↗
PubMed1986

Reconstitution of haemopoietic system with autologous marrow taken during relapse of acute myeloblastic leukaemia and grown in long-term culture.

In long-term cultures of bone marrow from a patient with acute myeloblastic leukaemia (AML) the leukaemic chromosome marker, which was present in a proportion of the marrow cells even during morphological remission, was not detectable after seven days of culture. After florid relapse of AML, large-scale bone marrow cultures were established while the patient received conditioning with cyclophosphamide and total body irradiation as for an allogeneic bone marrow transplant. Marrow cultured for ten days was reinfused and three and six months later the patient was in clinical remission with a normal karyotype.

Adolescent↗
PubMed1986

Alpha-2-interferon/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial.

Alpha-2-interferon (IFN) has demonstrable activity in advanced, relapsing, or refractory multiple myeloma. Because of the in vitro synergism between the IFNs and cytotoxic agents, we conducted a trial of 30 previously untreated patients with multiple myeloma utilizing various doses of alpha-2-IFN in combination with standard oral doses of melphalan and prednisone. The combination was well-tolerated without unusual or unexpected toxic effects. The limiting toxicity included dose-related myelosuppression, and alpha-2-IFN induced flu-like symptoms and fatigue. Response was seen in at least as many patients as would be expected with melphalan and prednisone alone. The maximal tolerated dose for a phase II-III trial was 5.0 X 10(6) IU/m2 of alpha-2-IFN in combination with standard doses of melphalan and prednisone. Future trials should utilize this dose of alpha-2-IFN with dose de-escalation according to tolerance.

Adult↗
PubMed1985

A prospective study of the treatment of high-grade histology non-Hodgkin's lymphoma involving the gastrointestinal tract.

Thirty-six patients presenting with stage II-IV primary gastrointestinal non-Hodgkin's lymphoma of high-grade pathology were treated in a prospective study from 1975 to 1983 with combined modality therapy. A complete response rate of 56% was obtained and the overall 5-yr survival rate was 36%. The 5-yr relapse-free survival rate of the complete remitters was 79%. Multivariate analysis revealed that the remission achieved (P less than 0.001) and the completeness of primary surgery (P = 0.018) would reliably predict the duration of overall survival. The finding of diffuse histiocytic histology (Rappaport) predicted longer relapse-free survival. The majority of deaths were related to intra-abdominal complications and not to disseminated lymphoma. Gastrointestinal tract non-Hodgkin's lymphoma of high-grade pathology of all stages is curable with a combination of chemotherapy and radiotherapy following surgery to remove as much macroscopic disease as is possible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Phase II study of recombinant alpha-2 interferon in resistant multiple myeloma.

A multicenter phase II study of INTRON, recombinant alpha-2 interferon (Schering Corp, Kenilworth, NJ), in patients with relapsing or refractory myeloma was initiated. Patients received either intravenous therapy for two weeks followed by subcutaneous therapy or subcutaneous dosing from initiation of treatment. Of 38 evaluable patients, 19 were refractory and 19 had relapsed at entry. Twenty-five of 38 had received prior treatment with multiple drugs. Responses were seen among 2/19 refractory patients and 5/19 relapsing patients. Three of seven responders continue to respond for more than one year while receiving maintenance therapy. Most patients experienced improvement in bone pain, and one patient, with a complete response, had healing of bone lesions. Survival curves show a statistically significant improvement in survival for responders v nonresponders. INTRON was well-tolerated with only four patients discontinuing treatment due to adverse effects. Thirty-two percent of patients had hematologic toxicity requiring dose adjustment; however, there was no evidence of cumulative hematologic toxicity. No patients developed serum neutralizing factors to interferon. Additional trials are warranted to study the activity of INTRON in previously untreated patients.

Adult↗
PubMed1985

Phase II trial of epirubicin in gastric cancer.

Patients with advanced inoperable or recurrent adenocarcinoma of the stomach received an iv bolus of epirubicin (75 mg/m2) every 3 weeks. Partial responses were observed in four of 24 evaluable patients (17%). Treatment was generally well tolerated; a drop in left ventricular ejection fraction was observed in one patient who had received 450 mg/m2 of epirubicin.

Adenocarcinoma↗
PubMed1985

Phase II study of rDNA human alpha-2 interferon in multiple myeloma.

This is a report of a phase II trial of rDNA human alpha-2 interferon (IFN) (Schering-Plough 30500) in previously treated patients with multiple myeloma. Patients received 2 megaunits/m2 of IFN by sc injection 3 days per week for 3 months. Responding patients continued receiving the same dose, but those with stable disease received 10 megaunits/m2 three times per week. Eighteen patients were treated. Two partial responses were seen, one at the lower dose and one at the higher dose. The lower dose was well tolerated, but three of six patients who received 10 megaunits/m2 had to stop treatment because of toxicity. Hematological toxicity was mild. At this dose and schedule, IFN has only minimal activity in previously treated patients.

Adult↗
PubMed1984

A phase I toxicity study of human rDNA interferon in patients with solid tumours.

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.

Blood↗
PubMed1984

A randomised study of adjuvant chemotherapy after mantle radiotherapy in supradiaphragmatic Hodgkin's disease PS IA-IIB: a report from the Manchester lymphoma group.

One hundred and fourteen untreated patients with pathological stage (PS) IA-IIB supradiaphragmatic Hodgkin's Disease were randomised to mantle radiotherapy alone (55) or mantle radiotherapy followed by 6 courses of adjuvant chemotherapy with mustine, vinblastine, prednisolone and procarbazine- MVPP (59). Patients excluded were those outside the age range 16-65 years and those with massive mediastinal disease precluding laparotomy. Bulk disease was defined as a mass of lymph nodes measuring five centimetres or more in any axis. Mediastinal bulk was present if the ratio of the maximum width of mediastinal disease to the maximal chest diameter was more than one third. All patients achieved a complete remission. Median duration of follow-up was 62 months (range 16-97). The relapse free survival (RFS) was 81%; 69% for radiotherapy alone and 93% for adjuvant chemotherapy (P = 0.002). RFS was also shown to be adversely affected by B symptoms (P = 0.0003), bulk disease (P = 0.018), abnormal CXR (P = 0.037), and increasing stage (P = 0.039). Age, sex, histology, and number of sites involved had no significant effect upon RFS. A Cox multivariate analysis showed that only three variables had a significant adverse effect on RFS - radiotherapy alone, the presence of bulk disease, and B symptoms. The overall 5 year survival was 93% with no statistically significant difference between the two treatment groups (P = 0.54). Survival was adversely affected by three variables - B symptoms (P = 0.02), the presence of bulk disease (P = 0.002), and pathological stage (P = 0.05). High risk groups for relapse are those with bulk and B symptoms. This analysis has shown that RFS was significantly improved by adjuvant chemotherapy, but that overall survival was not.

Adolescent↗
PubMed1984

Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial.

Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200 mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P less than 0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P less than 0.001).

Acyclovir↗
PubMed1984

Observations on the toxicity of the combination of gentamicin and mezlocillin in the treatment of patients with acute leukaemia.

In a retrospective study we have compared the toxic side effects related to the use of two antibiotic regimens in the treatment of febrile episodes in neutropenic, leukaemic patients undergoing first remission-induction. Nephrotoxicity was more severe in the gentamicin-mezlocillin (G/M) group: four patients developed oliguric renal failure and two others showed rises in the serum creatinine of more than 0.03 mmol/l. One of the two patients in the gentamicin-ticarcillin (G/T) group who showed nephrotoxicity developed renal failure. Ototoxicity and skin rashes were more commonly observed with G/M than with G/T, and the differences were statistically significant for both ototoxicity (P = 0.0004) and drug rashes (P = 0.02). The cause of the observed differences in toxicity has not been identified.

Acute Disease↗