Vinorelbine and infusional 5-fluorouracil in anthracycline and taxane pre-treated metastatic breast cancer.

AIMS: To evaluate the efficacy and toxicity of a combination of intravenous vinorelbine and 5-fluorouracil (5-FU) given by continuous infusion in the treatment of metastatic breast cancer previously treated with anthracyclines and taxanes. MATERIALS AND METHODS: Sixty-one patients with metastatic breast cancer were treated with intravenous vinorelbine 30 mg/m2 on days 1 and 8 of each 21-day cycle together with 5-FU 200 mg/m2/day by continuous infusion. All had previously been treated with an anthracycline and 41% had also been previously treated with a taxane. All had normal haematological, renal and hepatic function and all but three had an Eastern Cooperative Oncology Group performance score of 2 or better. RESULTS: The overall response rate by World Health Organization criteria was 46% (28 patients); excluding nine non-evaluable patients gave a response rate of 54%. In patients who had previously been treated with both an anthracycline and a taxane, a response rate of 50% was observed (12 of 24 patients). Severe toxicity was uncommon, as was toxicity attributable to infusional 5-FU. Myelosuppression was rarely severe, but was common and led to delay or dose reduction in 38% of treatments. Eleven patients (18%) were admitted with fever and/or neutropenia and one patient died. The median received dose intensity was vinorelbine 16 mg/m2/week and 5-FU 143 mg/m2/day. CONCLUSIONS: The combination of vinorelbine and infusional 5-FU is active in metastatic breast cancer, including in patients previously treated with an anthracycline and a taxane. Toxicity is generally manageable, but myelosuppression is significant at this dose regimen. Recommended doses for routine clinical use are 5-FU 200 mg/m2/day and intravenous vinorelbine 30 mg/m2 days 1 and 15 on a 28-day cycle.

Barriers to following dietary recommendations in Type 2 diabetes.

AIMS: To evaluate barriers to following dietary recommendations in patients with Type 2 diabetes. METHODS: We conducted focus groups and surveys in urban and suburban VA and academic medical centres. For the written survey, a self-administered questionnaire was mailed to a random sample of 446 patients with diabetes. For the focus groups, six groups of patients with diabetes (three urban, three suburban) were conducted, with 6-12 participants in each group. The focus groups explored barriers across various types of diabetes self-management; we extracted all comments relevant to barriers that limited patients' ability to follow a recommended diet. RESULTS: The written survey measured the burden of diabetes therapies (on a seven-point rating scale). Moderate diet was seen as a greater burden than oral agents (median 1 vs. 0, P = 0.001), but less of a burden than insulin (median 1 vs. 4, P < 0.001). A strict diet aimed at weight loss was rated as being similarly burdensome to insulin (median 4 vs. 4, P = NS). Despite this, self-reported adherence was much higher for both pills and insulin than it was for a moderate diet. In the focus groups, the most commonly identified barrier was the cost (14/14 reviews), followed by small portion sizes (13/14 reviews), support and family issues (13/14 reviews), and quality of life and lifestyle issues (12/14 reviews). Patients in the urban site, who were predominantly African-American, noted greater difficulties communicating with their provider about diet and social circumstances, and also that the rigid schedule of a diabetes diet was problematic. CONCLUSIONS: Barriers to adherence to dietary therapies are numerous, but some, such as cost, and in the urban setting, communication with providers, are potentially remediable. Interventions aimed at improving patients' ability to modify their diet need to specifically address these areas. Furthermore, treatment guidelines need to consider patients' preferences and barriers when setting goals for treatment.

Phase II study of gemcitabine as first-line chemotherapy in patients with advanced or metastatic breast cancer.

In this phase II study, the efficacy and tolerability of gemcitabine were studied in 42 patients with locally advanced or metastatic breast cancer who had received up to one prior chemotherapy regimen in an adjuvant setting. Ten patients had received adjuvant chemotherapy. Twenty-eight patients (67%) had visceral disease spread at entry. Gemcitabine (1000 mg/m2) was administered weekly on days 1, 8 and 15 of a 28-day cycle. The mean number of completed cycles was 3.9 and the mean dose delivered was 942.2 mg/m2. Ninety-seven percent of injections were administered as assigned. No complete responses were observed, but there were six partial responses and 24 patients with stable disease lasting 2-9 months. The overall response rate was 14.3% (95% CI 5.4-28.5%). The median survival for all patients was 15.2 months. Maximum WHO grade 3 and 4 toxicities were observed in five patients for nausea and vomiting, one patient for diarrhea, one patient for pain, seven patients for alanine transaminase, and eight patients for segmented neutrophils. There were no grade 3 and 4 toxicities for alopecia. These data confirm modest single-agent gemcitabine activity in advanced or metastatic breast cancer. Gemcitabine's favorable toxicity profile makes it an ideal candidate for combination chemotherapy.

Five-year follow-up of a prospective randomised multi-centre trial of weekly chemotherapy (CAPOMEt) versus cyclical chemotherapy (CHOP-Mtx) in the treatment of aggressive non-Hodgkin's lymphoma. Central Lymphoma Group.

BACKGROUND: Weekly alternating regimen known as CAPOMEt is compared to standard cyclical chemotherapy (CHOP-Mtx) in aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Three hundred and eighty-one patients with aggressive NHL were randomised to receive either cyclophosphamide, doxorubicin, vincristine, prednisone and methotrexate (CHOP-Mtx) on a cyclical basis or a weekly regimen incorporating the same drugs with the addition of etoposide (CAPOMEt). RESULTS: After pathological review, 281 patients were deemed eligible. At the census date of 31 March 1994, 158 patients were alive with a median follow up of 5.9 years (minimum 3.0 years). Analysis of all patients and eligible patients showed no significant treatment differences in the rates of complete remission (CR), failure free survival (FFS) or overall survival (OS) between the two arms. The actuarial median OS was 24 months for CAPOMEt compared with 31 months for CHOP-Mtx, with five-year actuarial survival rates of 37% and 43%, respectively. Myelosuppression was significantly more severe with CHOP-Mtx and neurotoxicity was much more common with CAPOMEt. CONCLUSION: Weekly CAPOMEt is equally effective as standard cyclical CHOP-Mtx treatment in aggressive NHL.

A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer.

139 peri- and postmenopausal women with advanced or recurrent breast cancer who had not received prior hormonal therapy were randomised in an open, cross-over study comparing the synthetic progestogen megestrol acetate with tamoxifen. The response rate (CR/PR) to megestrol acetate (25%; 95% confidence interval (CI) 15-35%) was not significantly different from that produced by tamoxifen (33%, CI 22-44%). Time-to-treatment failure was also similar in the two groups. Cross-over treatment was given on progression in 76 cases. Cross-over response (CR/PR) was seen in 3 of 35 patients (9%) receiving megestrol acetate as second-line therapy and in 6 of 41 patients (15%) receiving tamoxifen second-line. There was no significant difference in survival between the groups (P = 0.17) with median survival times of 24 and 32 months for the megestrol acetate and tamoxifen groups, respectively. The toxicity profile of the two drugs was different, although significant toxicity was rare with either agent. Megestrol acetate is an effective treatment for advanced breast cancer in older women when used either as first- or second-line treatment. Cross-over response is seen following both treatments. Given that most patients now receive tamoxifen as adjuvant treatment, megestrol acetate would appear to be one of the logical choices for patients who find the side-effects of tamoxifen unacceptable and for those who relapse on tamoxifen with further hormone therapy being clinically indicated.

ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central Lymphoma Group.

PURPOSE: The United Kingdom Central Lymphoma Group (CLG) has modified mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) by substituting mechlorethamine with chlorambucil and dacarbazine with etoposide in the treatment of patients with advanced Hodgkin's disease (HD). Prednisolone is included in the bleomycin-containing combination, and the vinca alkaloids have been switched to balance the myelotoxicity of the two component regimens. PATIENTS AND METHODS: The resulting ChlVPP/PABlOE regimen is as follows: on days 1 to 14, chlorambucil 6 mg/m2 orally, procarbazine 100 mg/m2 orally, and prednisolone 30 mg/m2 orally; on days 1 and 8, vinblastine 6 mg/m2 intravenously (i.v.); on day 29, doxorubicin 40 mg/m2 i.v.; on days 29 and 36, vincristine 1.4 mg/m2 (maximum, 2 mg) i.v., and bleomycin 10 mg/m2 i.v.; on days 30, 31, and 32, etoposide 200 mg/m2/d orally; on days 29 to 43, inclusive, prednisolone, 30 mg/m2 orally. The second full cycle restarts on day 50. Treatment continues to maximum response plus two full cycles, but with a minimum of three full cycles. Radiotherapy is administered, after chemotherapy, to sites of previously bulky disease. Since 1983, 216 patients with previously untreated, advanced Hodgkin's disease (HD) have entered this study. RESULTS: The complete remission (CR) rate after chemotherapy was 73% (95% confidence interval [CI], 67% to 79%), and after additional radiotherapy was 85% (95% CI, 80% to 90%). The failure-free survival (FFS) rate at 5 years was 68% (95% CI, 61% to 74%), and the overall actuarial survival at 5 years was 78% (95% CI, 72% to 84%). The CR rate in patients in the poorer prognostic categories was high: 81% in patients with albumin levels less than 37 g/L, 79% in patients older than 40 years of age, 84% in stages IIIB plus i.v. disease, and 79% in patients presenting with B symptoms. As expected, nausea and vomiting were not major problems, although infection, often in the context of myelosuppression, complicated almost half the cases, and 29% of patients required admission at some stage for treatment of infection. CONCLUSION: In this multicenter study, ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but with less nausea and vomiting. Treatment duration was shorter than in the original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B (CALGB) trial. It will now be compared with PABlOE alone.

A phase I study of the left-shifting agent BW12C79 plus mitomycin C and the effect on the skeletal muscle metabolism using 31P magnetic resonance spectroscopy.

BW12C79 stabilizes the oxyhemoglobin molecule resulting in a reversible left-shift of the oxygen saturation curve. The activity of a number of bioreductive anticancer drugs, such as mitomycin C, may be enhanced under hypoxic conditions. Twenty-four patients with various malignancies received BW12C79 and mitomycin C. BW12C79 was administered i.v. with a loading dose (20-50 mg/kg) over 1 h followed by a maintenance infusion of 4 mg/kg/h for 5 h. Percentage modification of the oxyhemoglobin (degree of left-shift) was dose related with maximum modification of 56% and was maintained for the duration of maintenance infusion of BW12C79. Hemoglobin electrophoresis showed a fast moving band consistent with the BW12C79-oxyhemoglobin complex. Side effects at the top dose level comprised headache, nausea/vomiting, vein irritation, and myocardial ischemia. One other patient suffered from an acute encephalopathy of unknown etiology a few days following BW12C79. 31P magnetic resonance spectroscopy of exercising calf muscles showed increased breakdown of high energy phosphate stores and a greater reduction in pH. Recovery of the high energy phosphate stores after exercise was slow. These results were consistent with reduced oxygen supply due to either a left shift of the oxygen saturation curve and/or reduced muscle blood flow. BW12C79 did not interfere with the pharmacokinetics of mitomycin C. In conclusion, this phase I study demonstrates the feasibility of achieving a significant left shift in the oxygen saturation curve in cancer patients which is maintained for at least 5 h with acceptable toxicity. The maximum tolerated dose of BW12C79 was 50 mg/kg loading infusion followed by a maintenance infusion of 4 mg/kg/h. Magnetic resonance spectroscopy results were consistent with reduced supply of oxygen to exercising skeletal muscle. BW12C79 may be of potential benefit as an adjunct to bioreductive drugs in the treatment of solid tumors.

Phase I study of bryostatin 1: assessment of interleukin 6 and tumor necrosis factor alpha induction in vivo. The Cancer Research Campaign Phase I Committee.

BACKGROUND: Many oncogenes have been shown to code for growth factor receptors that are involved in regulation of cell growth and proliferation and can activate transcription via protein kinase C. Bryostatin 1, a partial agonist of protein kinase C, has demonstrated potent antitumor activity in vitro and in vivo in human tumor xenografts. PURPOSE: The aim of this phase I study was to determine the optimal dosage and toxicity profile of bryostatin 1 and its influence on cytokine release in vivo. METHODS: Three successive cohorts consisting of 35 patients with various malignant tumors were treated with bryostatin 1 by intravenous infusion over 1 hour as follows: cohort A--35 micrograms/m2 (three patients) or 50 micrograms/m2 (eight patients) once every 2 weeks; cohort B--25 micrograms/m2 once a week (eight patients); and cohort C--25 micrograms/m2 once a week for 3 weeks, with no treatment during the 4th week (16 patients). Plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) were measured by immunoradiometric assay and by radioimmunoassay, respectively. RESULTS: The dose-limiting toxicity was grade 3 or 4 myalgia in four of 11 patients in cohort A, in two of eight in cohort B, and in none of 16 in cohort C. Occurrence of myalgia was dose related. There was no significant myelosuppression, apart from a small and transient fall in platelet count. Six patients experienced acute but transient skin flushing, dyspnea, hypotension, and bradycardia, probably related to the bryostatin 1 vehicle. TNF-alpha and IL-6 were detected in plasma at 2 and 24 hours after treatment, respectively, and the levels were dose related (P = .02). Two patients with metastatic malignant melanoma had partial remission after three or four cycles of therapy; remission lasted 6 weeks and 10+ months, respectively. CONCLUSIONS: The dose-limiting toxicity of bryostatin 1 was myalgia. Plasma IL-6 and TNF-alpha concentrations were increased within 24 hours of therapy. Antitumor activity against malignant melanoma was observed early in the course of treatment. IMPLICATIONS: The recommended dosage of bryostatin 1 for phase II studies is 25 micrograms/m2 by intravenous infusion for 1 hour once a week for 3 weeks, with no treatment in the 4th week. IL-6 and TNF-alpha plasma concentrations may be useful in monitoring biological activity of bryostatin 1. Future studies should explore use of this drug with other conventional immune modulators and conventional cytotoxic drugs.

Differential modulation of doxorubicin toxicity to multidrug and intrinsically drug resistant cell lines by anti-oestrogens and their major metabolites.

The ability of the anti-oestrogens tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites to modify doxorubicin (dox) toxicity to intrinsically resistant and multidrug resistant cell lines was compared, using human breast and lung cancer, and Chinese hamster ovary cell lines. The anti-oestrogens significantly enhanced dox toxicity to multidrug resistant, P-glycoprotein-positive cell lines, but did not affect toxicity to intrinsically resistant, P-glycoprotein-negative cells. Modification was observed at clinically achievable anti-oestrogen concentrations. Toremifene and tamoxifen would therefore appear to be good candidates for in vivo studies as MDR modulating agents in selected patients with P-glycoprotein-positive tumours.

Association between expression of activated 72-kilodalton gelatinase and tumor spread in non-small-cell lung carcinoma.

BACKGROUND: Matrix metalloproteinases, in particular the 92-kd and 72-kd gelatinases, have been implicated in the progression of breast, colorectal, and gastric carcinomas, but involvement of the gelatinases in progression of non-small-cell lung carcinoma has not been documented. Immunohistochemical studies have measured the overall expression of these enzymes in tumor tissue but have failed to determine the proportion of active enzyme to latent proenzyme. Because the conversion of the latent proenzyme to active enzyme results in removal of a 10-kd amino-terminal domain, the expression of each proteinase can be determined by zymography, which separates substances according to molecular weight. PURPOSE: The purpose of this study was to examine the expression and activation of 92-kd and 72-kd proenzymes in non-small-cell lung carcinoma. METHODS: Gelatin zymography was used to study the expression of 92-kd and 72-kd gelatinases in 22 samples of non-small-cell lung carcinoma and adjacent uninvolved tissue. Medium conditioned by human RPMI-7951 melanoma cells was used as a marker for the 72-kd proenzyme, and medium conditioned by concanavalin A-treated human HT-1080 fibrosarcoma cells was used as a marker for both the 92-kd proenzyme and the 62-kd activated form of the 72-kd proenzyme. RESULTS: Both 92-kd and 72-kd proenzymes were expressed to varying degrees in the samples studied. The 82-kd activated form of the 92-kd proenzyme was detected in eight tumor samples but in none of the matched uninvolved tissues. Expression of the 62-kd activated form of the 72-kd proenzyme ranged from a strong band in the tumor tissue, with little or none detectable in the adjacent uninvolved tissue, to the presence of only trace amounts of enzyme in both tumor and uninvolved tissue. There was, however, a highly significant statistical association between the level of expression of the 62-kd activated enzyme in the tumor tissue and evidence of tumor spread (P = .001). CONCLUSION: These results demonstrate elevated expression of the activated forms of both the 92-kd and 72-kd proenzymes in non-small-cell lung carcinoma tissue relative to adjacent uninvolved tissue. IMPLICATION: These results indicate that non-small-cell lung carcinoma should be considered as a possible target for metalloproteinase inhibitory therapy.

Selective reversal of vinblastine resistance in multidrug-resistant cell lines by tamoxifen, toremifene and their metabolites.

In this study we describe the effects of tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites on the toxicity of a range of drugs to human breast and lung cancer and to Chinese hamster ovary cell lines, determined using a tetrazolium-based semi-automated colorimetric assay. Vinblastine resistance was completely abolished in an mdr1-transfected lung cancer cell line (S1/1.1), indicating that P-glycoprotein-mediated multidrug resistance can be fully reversed by anti-oestrogens. A substantial (14- to 39-fold) enhancement of vinblastine toxicity to highly multidrug-resistant (MCF-7Adr) cells expressing P-glycoprotein was also observed in the presence of tamoxifen, toremifene and their metabolites, while m-amsacrine, cisplatin and melphalan toxicity was unaffected.

High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects and in vitro assessment in p-glycoprotein expressing cell lines.

Twenty-six patients with relapsed or drug-resistant cancer were treated with a combination of oral etoposide (300 mg day-1 for 3 days) and high-dose oral tamoxifen as a potential modulator of drug resistance (480 or 720 mg day-1 for 6 days beginning 3 days before etoposide). One patient with relapsed high-grade lymphoma and one with adenocarcinoma of unknown primary site has a partial response. Toxicity consisting of nausea, vomiting and subjective dizziness, unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum levels of tamoxifen averaged 3-3.5 microM on day 4 of all courses of treatment at both 480 and 720 mg day-1. N-desmethyltamoxifen levels were lower than tamoxifen during the first course (2 microM) but increased to equal tamoxifen levels during the second course. Didesmethyltamoxifen levels remained below 1 microM. In vitro, both tamoxifen and the standard modulator of multidrug resistance, verapamil, produced minor enhancement of etoposide cytotoxicity in the MCF-7 wt cell line but produced no enhancement with any other cell line. High, intermittent doses of tamoxifen can be given with acceptable toxicity and produce serum levels that have been shown to modulate drug resistance in vitro. In vitro, however, such levels have no significant effect on etoposide cytotoxicity towards a range of wild-type and MDR cell lines.

Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856).

Temozolomide (CCRG 81045: M&B 39831: NSC 362856) is an analogue of mitozolomide displaying similar broad spectrum activity in mouse tumours, but showing considerably less myelosuppression in the toxicology screen. Temozolomide was initially studied intravenously at doses between 50-200 mg m-2 and subsequently was given orally up to 1,200 mg m-2. A total of 51 patients were entered on the single dose schedule. Temozolomide exhibits linear pharmacokinetics with increasing dose. Myelotoxicity was dose limiting. Experimentally, temozolomide activity was schedule dependent and therefore oral administration was studied as a daily x 5 schedule between total doses of 750 and 1,200 mg m-2 in 42 patients. Myelosuppression was again dose limiting. The recommended dose for Phase II trials is 150 mg m-2 po for 5 days (total dose 750 mg m-2) for the first course, and if no major myelosuppression is detected on day 22 of the 4 week cycle, the subsequent courses can be given at 200 mg m-2 for 5 days (total dose 1 g m-2) on a 4 week cycle. Mild to moderate nausea and vomiting was dose related but readily controlled with antiemetics. Clinical activity was detected using the 5 day schedule in four (2CR, 2PR; 17%) out of 23 patients with melanoma and in one patient with mycosis fungoides (CR lasting 7 months). Two patients with recurrent high grade gliomas have also had partial responses. Temozolomide is easy to use clinically and generally well tolerated. In the extended Phase I trial temozolomide only occasionally exhibited the unpredictable myelosuppression seen with mitozolomide.

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.

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.

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%.

Correlation of morphology, immunophenotype, and flow cytometry with remission induction and survival in high grade non-Hodgkin's lymphoma.

A series of cases of high grade non-Hodgkin's lymphomas has been studied by morphology (110 cases), immunocytochemistry (90 cases), using reagents reactive in fixed paraffin-embedded tissue, and flow cytometry (77 cases). B-cell tumours constituted 67.0 per cent of the total, T-cell tumours 22.0 per cent, and unclassified cases 8.8 per cent. Immunocytochemistry revealed two anaplastic carcinomas. Of the 77 cases studied by flow cytometry, 67.5 per cent were diploid and 32.5 per cent DNA aneuploid. T-cell tumours were more likely to be diploid than B-cell tumours, though the difference did not reach statistical significance. T-cell tumours had a significantly lower proliferative index (%S + G2) than B-cell tumours (P = 0.002). The overall remission induction rate was 68 per cent and actuarial 3-year survival 47 per cent. There was a trend for cases with %S + G2 less than 22 per cent to survive longer (P = 0.07). This trend became statistically significant when aneuploid cases were added to the high PI group (P = 0.04). No correlation was seen between morphological or immunophenotypic groups and remission induction rates or survival.