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Biomedical subjects

M H Cullen

Publications and source records attributed to M H Cullen.

At least 55 records · Page 3Linked to original sources
PubMed1991

Assessment of the response to chemotherapy in oesophageal cancer.

Thirty-eight patients with localised oesophageal carcinoma have been studied by computed tomography (CT) and barium swallow before and after preoperative chemotherapy and the results correlated with the pathological findings in the resected specimen. Overall 48% of patients showed a complete or partial response to chemotherapy on CT, compared with 50% on barium and 94% on pathological examination. This study highlights deficiencies in CT scanning and barium swallow as methods of assessing the regression of tumor bulk following chemotherapy for oesophageal carcinoma. We suggest that strict and specific criteria will have to be laid down before the results of chemotherapy in this disease can be reliably and accurately evaluated.

Aged↗
PubMed1991

A phase II study of 5-fluorouracil, adriamycin and mitomycin-C in adenocarcinoma of the oesophagus.

We have evaluated the effect of 5-fluorouracil 600 mg/m2, doxorubicin ('Adriamycin') 40 mg/m2, and Mitomycin-C 4 mg/m2 (FAM) in two groups of patients with adenocarcinoma of the oesophagus, as either a preoperative or primary treatment. Response was assessed by barium swallow, CT scan, and measurement of metastases where present. Toxicity was as reported for FAM in gastric cancer. In the operated group 8 of 22 patients (36%) showed a partial response following two courses of FAM. Resection was completed in 20 patients, with six hospital deaths (30%). Of the 14 patients who were discharged from hospital, 8 have died (median 8 months) and 6 are alive at 12 to 27 months, with known recurrence in 1. In the non-operated group 6 of 17 patients (35%) showed a response, one complete, following one to six (mean 4.2) courses of FAM. Fifteen patients have died (median 5 months), and 2 are alive and free from disease at 12 and 17 months. Neoadjuvant therapy with FAM in adenocarcinoma of the oesophagus offers no advantage over surgery alone, although with inoperable disease FAM may be of use in palliation.

Adenocarcinoma↗
PubMed1991

A case of spontaneous regression of metastatic testicular teratoma.

We report the apparently spontaneous regression of metastatic disease in a young man who had previously undergone orchidectomy for a primary testicular teratoma. Serial serum tumour marker estimations revealed a sharp rise followed by a spontaneous decline in levels in a patient who had requested that chemotherapy be deferred for personal reasons.

Adult↗
PubMed1990

Quality of life after treatment for testicular cancer--the patient's view.

Twenty-eight patients cured of testicular cancer by cisplatin-based chemotherapy were asked for their own views of the long-term psychological and social effects of their treatment. Their views were compared with a group of 34 testicular cancer patients cured by radiotherapy who were matched for age, social class and time since treatment. A category rating type questionnaire was used with questions concerning general health, subjective side-effects of treatment, employment, relationships, reproduction and mood. The principal differences were (1) the chemotherapy group reported a greater prevalence of physical side-effects, (2) the radiotherapy group reported greater anxiety and depression since treatment and (3) a significant number of patients in the chemotherapy group felt that their illness had had beneficial effects on their relationships with family and friends.

Adult↗
PubMed1990

Long-term toxicity of chemotherapy for testicular cancer--the cost of cure.

Twenty-seven patients cured of advanced testicular cancer by cisplatin-based chemotherapy have been assessed, a median of 30 months after start of treatment, for the long-term effects of such treatment on renal, endocrine, audiometric, reproductive and respiratory function. To control for the effects of orchidectomy on endocrine function a similar group of 11 patients cured by orchidectomy alone was also assessed. The extents of impairment in hearing and renal function were related to the total dose of cisplatin received, while the majority of patients had respiratory impairment which was, in part, related to the total dose of bleomycin. TSH was significantly higher in the chemotherapy group although serum free thyroxine and free T3 were normal in all. FSH was raised in 67% of the chemotherapy group although serum free thyroxine and free T3 were while LH was raised in 75% and 45% respectively. Serum testosterone was normal in all. The levels of FSH and LH were both independently correlated with age of the patient while FSH was higher in patients having more chemotherapy and had a tendency to fall towards normal with time since treatment. Over half the patients had normal sperm concentrations although 74% had a raised proportion of abnormal sperm. Indices of sperm function were worse in patients having more chemotherapy but sperm number increased towards normal with time since treatment, particularly after the second year. The long-term side-effects of chemotherapy for testicular cancer are thus generally mild but are largely irreversible and their severity is related to the total amount of chemotherapy received. As their longer term significance is not clear we would recommend that, in the treatment of testicular cancer, doses of chemotherapy are reduced to the minimum required for cure. Assessment of long-term side-effects of chemotherapy for testicular cancer should be a mandatory part of any study of such treatment and should be considered in any comparison of different therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Ifosfamide, mitomycin and radiotherapy in non-small-cell lung cancer.

Ifosfamide and mitomycin C are two of the more active single agents in non-small-cell lung cancer (NSCLC). This study evaluates these drugs in combination followed by radiotherapy. A total of 33 ambulatory patients with inoperable NSCLC were treated with 5 g/m2 ifosfamide as a 24-h infusion, with the concurrent administration of sodium 2-mercaptoethane sulphonate (mesna; 160% of the ifosfamide dose) and 6 mg/m2 mitomycin C given as an i.v. bolus injection on the 2nd day. The median age of the patients was 61 years. In all, 20 patients had limited disease and 13, extensive disease. A total of 30 were assessable for response to chemotherapy, 8 of whom achieved a partial response (PR) and 5, a complete response (CR) (2 were verified bronchoscopically). The overall response rate was thus 43%. All but one response (a PR) were in patients with limited disease (LD). A total of 21 patients, including 13 responders, received thoracic irradiation (30 Gy in 8 fractions over 10 days) following chemotherapy. One PR was converted to a radiological CR. In all, 17 (55%) of the patients were alive at 1 year. All patients suffered chemotherapy-induced alopecia (WHO grade 3), but there were no treatment modifications due to myelosuppression, haemorrhagic cystitis or other toxicity. WHO grade 3 nausea and vomiting were seen in all patients. There was one treatment-related death. Combination therapy using ifosfamide and mitomycin C has useful activity in NSCLC.

Adult↗
PubMed1989

The role of metoclopramide in acute and delayed chemotherapy induced emesis: a randomised double blind trial.

High dose metoclopramide is an effective anti-emetic for use with cisplatin containing chemotherapy regimens but can cause extrapyramidal reactions. Lorazepam and dexamethasone are increasingly being used to alleviate chemotherapy induced emesis. This trial has assessed the contribution of high dose metoclopramide to anti-emetic control when given with dexamethasone and lorazepam. Eight-one patients receiving chemotherapy, mainly for gynaecological malignancy, entered a randomised double blind cross-over trial comparing dexamethasone and lorazepam with or without a 24 h metoclopramide infusion. This was followed by oral dexamethasone with or without oral metoclopramide for three further days depending on the initial randomisation. Sixty-one patients were fully evaluable. Fifty-five received cisplatin containing regimens and six non-cisplatin regimens. There was a significant reduction in the number of episodes of vomiting during the first 24 h in patients receiving the metoclopramide combination (P = 0.0001). On first exposure to chemotherapy 45% of patients receiving dexamethasone, lorazepam and high dose metoclopramide had no vomiting while 67% had two episodes or less ('major control'). This compared to 11% total control and 25% major control in those receiving dexamethasone, lorazepam and placebo. The control of nausea in the first 24 h was also improved (P = 0.0001). There was no difference in the degree of nausea or vomiting during the following three weeks between those receiving oral dexamethasone alone and those receiving dexamethasone and metoclopramide. Both groups showed a significant increase in nausea in the three weeks following the second course of treatment when compared to the first (P = 0.0007). Extrapyramidal reactions were recorded in 11.5% of patients receiving metoclopramide. More patients stated a preference for the metoclopramide combination although this was not statistically significant (chi 2(1) = 0.29, P = 0.59). In conclusion the combination of dexamethasone and lorazepam can give major control of emesis in 25% of patients receiving very emetogenic chemotherapy. The addition of metoclopramide increases this to 67% on first exposure to chemotherapy, but at the expense of extrapyramidal reactions in 11.5%.

Adult↗
PubMed1989

Chemotherapy plus adjuvant surgery for local small cell lung cancer.

Eight patients with local Stage II (T2N1) and III (T3N0, T3N1, T2N2) small cell lung cancer received combination chemotherapy prior to elective surgery to assess the effectiveness of such a regimen in improving operability, preventing local relapse and extending survival. The regimen was well tolerated and prevented local relapse. However, the median time to recurrence of disease was 10 months and the median survival time 13 months, results which are similar to those achieved with chemotherapy and radiotherapy. Distant metastases, particularly in the brain, occurred predictably indicating that successful adjuvant surgery, despite preventing local relapse, may not afford additional survival benefit with currently available drug regimens.

Adult↗
PubMed1988

A phase II study of oral idarubicin (4-demethoxydaunorubicin) in advanced breast cancer.

Idarubicin (4-demethoxydaunorubicin: DMDNR) is an orally active analogue of daunorubicin that has shown promising activity in animal and early clinical studies. We gave idarubicin in a phase II study to patients with advanced breast cancer unresponsive to hormonal manipulation and in some cases to standard chemotherapeutic agents. Idarubicin was given orally every 21 days at a starting dose of 40 mg/m2 with dose escalation until myelosuppression occurred. Nadir blood counts showed that patient compliance was good. Of 33 patients studied, 32 are evaluable for response: 4 (13%) had partial responses (95% confidence interval 1%-23%) with a duration of response between 32 and 59 weeks; 8 (25%) had static disease for between 17 and 48 weeks; and 20 failed to respond. For patients not previously exposed to chemotherapy, the response rate was 3/19 (16%). Toxicity was mild, with little or no gastro-intestinal disturbance in the majority of patients, no severe haematological toxicity and little alopecia. Two patients however, were withdrawn from the study because of toxicity; one with a skin rash and one with severe vomiting. Idarubicin produces little toxicity when given orally at a dose of 40 mg/m2 every 21 days, but its activity in breast cancer is insufficient to justify its further use with this schedule. Further studies should be undertaken only if direct comparison can be made with doxorubicin.

Adult↗
PubMed1988

Mitomycin, ifosfamide and cis-platin in non-small cell lung cancer: treatment good enough to compare.

Mitomycin, ifosfamide and cis-platin are three of the most active single agents in the chemotherapy of non-small cell lung cancer. We have combined them for a phase 2 study in patients with inoperable non-small cell lung cancer. The regimen ('MIC') comprised: mitomycin 6 mg m-2, ifosfamide 3 g m-2 and cis-platin 50 mg m-2, with routine use of lorazepam, dexamethasone and high dose metoclopramide for anti-emesis. Seventy-four ambulatory patients with untreated, limited (LD) or extensive (ED) disease have entered this study, and 66 are evaluable for response. Thirty patients (45%) have achieved partial remission and 7 (11%) complete remission, as assessed radiologically. The overall response rate is thus 56% (95% confidence interval 44%-68%). There have been 29/43 responses in LD (67%, 95% CI 53%-81%) and 8/23 in ED (35%, 95% CI 15%-55%). The median response duration, measured from the start of treatment is 8.75 months. The median survival for the whole group is 9.2 months. The principal toxicity was nausea and vomiting which was severe or prolonged (greater than 48 h) for one or more courses, in 9% of patients. Performance status (PS) and weight were assessed before, and 3 weeks after the last course of chemotherapy. Fifteen (of 31 evaluable) responders improved their PS and only 1 responder deteriorated. Twenty-one of the 28 evaluable non-responders had no change in PS. The difference in PS change between responders and non-responders is highly significant (P = 0.002). Thirty evaluable responders experienced a mean increase in weight of 2.9% with treatment, whereas 24 evaluable non-responders had a mean weight loss of 3.8%. This change is also highly significant (P = 0.0013). MIC is clearly a well tolerated regime and among the most active combinations in non-small cell lung cancer. It will now be tested in a randomized trial against no chemotherapy.

Adult↗