Continuous versus intermittent tamoxifen versus intermittent/alternated tamoxifen and medroxyprogesterone acetate as first line endocrine treatment in advanced breast cancer: an EORTC phase III study (10863).

BACKGROUND: Continuous ligand depletion of endocrine responsive tumours may enhance resistance to therapy. Intermittent treatment with tamoxifen (T) was considered to mimic (incomplete) ligand depletion and reintroduction. Furthermore it was postulated that alternating tamoxifen with a non-cross resistant endocrine modality could (further) postpone hormone resistance. PATIENTS AND METHODS: Postmenopausal patients with advanced breast cancer who did not progress after 4 months of first line T therapy were randomised to continue T (40 mg daily) or to 2 monthly intermittent T or intermittent/alternated T and medroxyprogesterone acetate (MPA, 300 mg daily). At progression during break or during MPA, T should be reintroduced. Endpoints of the study were progression free survival (PFS), time to resistance to tamoxifen and overall survival (OS). RESULTS: Of 593 registered patients, 276 were randomised. After 8 years follow-up the median PFS for continuous T, intermittent T and intermittent/alternated T and MPA was 11.0 (8.1-15.2), 8.0 (6.2-12.4) and 10.8 (7.1-16.7) months, respectively (NS). Resistance to tamoxifen was established only in 84%, 70% and 55% of patients in the three treatment arms, respectively. The median times from randomisation to resistance to tamoxifen were 12.5 (9.1-21.1), 13.2 (8.8-19.8) and 24.0 (16.9-60.9) months, respectively (p<0.001), without translation in differences in survival times. CONCLUSION: Intermittent T or intermittent/alternated T and MPA had no impact on PFS or OS as compared with classical continuous T in patients with advanced breast cancer. Intermittent/alternated T and MPA resulted in prolonged time to resistance to T, but this might partly be due to bias by omittance of the proof of tamoxifen resistance in a high proportion of the patients in this treatment arm.

Breast cancer in Rubens paintings.

Rubens was one of main baroque painters who practices realism, which means that he painted whatever his eyes capture. That fact has helped us with the visual aspect and the circumstances where such paintings were painted. This has allowed us to discover alterations in the breast of the models he painted, which suggest breast cancer. Such painting are 'The three Graces', 'Diana and her nymphs pursued by satyrs', 'Orpheus and Euridice'. In 'The three Graces' we can see that the model on the right has an open ulcer with reddening of the skin, nipple retraction, reduction of breast volume as well as axilar lymph nodes. This is a visual aspect of a locally advanced breast cancer. In Diana and her nymphs pursued by satyrs and in Orpheus and Euridice we can see a breast retraction in the same place as in 'The three Graces', which suggest breast cancer indirectly. The analysis of the tumor mass in the models of these pictures allow us to know more on the works, the social environment and the diseases happened in the years this painter lived.

Increased conventional chemotherapy does not improve survival in multiple myeloma: long-term results of two PETHEMA trials including 914 patients.

BACKGROUND: Melphalan and prednisone (MP) has been the standard treatment for multiple myeloma (MM) for the last 30 years. Combination chemotherapy at conventional doses has not shown a significant prolongation of survival when compared to MP. There are few data comparing conventional chemotherapy at standard doses with conventional treatment at higher doses. We present the long-term outcome of 914 patients from two randomized trials comparing three different dose intensity regimens. METHODS: From 1 January, 1985 to 31 December, 1989, 487 patients were randomized between MP (melphalan 9 mg/m(2) p.o. and prednisone 60 mg/m(2) days 1-4) and alternating VCMP (vincristine 1 mg i.v. on day 1, cyclophosphamide 500 mg/m(2) i.v. on day 1, melphalan 6 mg/m(2) p.o. on days 1-4, and prednisone 60 mg/m(2) on days 1-4) and VBAP (vincristine 1 mg i.v. on day 1, BCNU and doxorubicin 30 mg/m(2) i.v. each on day 1, and prednisone 60 mg/m(2) on days 1-4). From 1 January, 1990 to 31 May, 1994, 427 patients were randomized between VCMP/VBAP at the above detailed doses (VCMP/VBAP 'SD') and the same regimen increasing the doses of cyclophosphamide and doxorubicin from 500 to 1200 mg/m(2) and from 30 to 50 mg/m(2), respectively (VCMP/VBAP 'HD'). RESULTS: Increasing dose intensity produced a significantly higher partial response rate (31% vs 45% vs 51% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P < 0.01). However, a significantly early death rate was observed in the HD arm (7.7, 7.5 and 12.1% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = 0.05). Median duration of response (20 vs 18 vs 19 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) and median survival (25 vs 31 vs 29 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) were similar in the three groups. MP produced a higher degree of thrombocytopenia than combination chemotherapy at standard (P = 0.002) or high dose (P = 0.01), this leading to a significantly higher dose reduction in the MP arm (P < 0.001 and P = 0.003 for VCMP/VBAP 'SD' and VCMP/VBAP 'HD', respectively). CONCLUSION: In these trials the response rate significantly correlated with the regimen intensity. However, no significant differences in response duration and survival were found. This highlights the limited role of conventional chemotherapy in MM and the need for further trials, aimed at determining the impact of new treatment approaches such as high-dose therapy/autotransplantation.

C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients.

UNLABELLED: C-erbB-2, CEA and CA 15.3 serial serum determinations were performed in 250 patients (follow-up: 1-4 years, mean 2.5 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Ninety-five patients developed metastases during follow-up. RESULTS: Abnormal c-erbB-2, CEA and CA 15.3 serum levels (> 20 U/ml, > 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis were found in 28.4%, 31.6% and 46.3% of the 95 patients with recurrence, with a lead time of 4.2 +/- 2.4, 5.0 +/- 2.5 and 4.6 +/- 2.7 months, respectively. One of the tumor markers was the first sign of recurrence in 69.5% of the patients. Tumor marker specificity was 100% with levels lower than the cut-point in all 155 patients without recurrence. Tumor marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver or bone metastases. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (10/12, 83.3%) than in those without overexpression (1/34, 2.9%) (p = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PgR+ patients (CA 15.3) or in PgR- patients (C-erbB-2) (p < 0.015). In conclusion, tumor markers are useful tools for the early diagnosis of metastases, being the first sign of recurrence in 69.5% of patients with relapse (76.3% in patients with metastases).

Prognostic significance of the detection of circulating malignant cells by reverse transcriptase-polymerase chain reaction in long-term clinically disease-free melanoma patients.

The purpose of this study was to assess the prognostic significance of the detection of circulating melanoma cells by reverse transcriptase-PCR in long-term clinically disease-free melanoma patients. Patients with melanoma who were free of clinical relapse for at least 6 months after primary tumor diagnosis were included and prospectively followed. Tyrosinase mRNA in peripheral blood from these patients was assayed by reverse transcriptase-PCR at the time of their inclusion in the study. One hundred six blood samples from 57 melanoma patients were analyzed. The median time between melanoma diagnosis and inclusion in the study was 24 months (range, 7-51 months). The median follow-up time calculated from the time of inclusion in the study was 27 months (range, 11-36 months). Tyrosinase mRNA in blood was detected in 10 (17.5%) of 57 patients: 2 (18%) of 11 stage I patients, 6 (19%) of 33 stage II patients, and 2 (15%) of 13 stage III patients. Actuarial 2-year DFS was 89% for the tyrosinase-negative patients versus 30% for the positive patients (P = 0.003). Actuarial 2-year OS was 97% for the tyrosinase-negative patients versus 72% for the positive patients (P = 0.001). Tyrosinase mRNA could be detected in the blood of a proportion of long-term disease-free melanoma patients, regardless of their initial clinical stage. The presence of late circulating melanoma cells in this selected group of clinically disease-free patients was significantly associated with a subsequent high risk of relapse and death.

Age: a critical factor in cancer management. A prospective comparative study of 400 patients.

BACKGROUND: older people are often excluded from cancer treatments solely on the grounds of age. AIMS: to compare cancer treatment in older and younger patients. PATIENTS AND METHODS: between June 1992 and September 1994, 400 cancer patients were included in this prospective comparative study. The factors compared between younger and older subjects were performance status, associated chronic diseases, delay in diagnosis, stage of disease and initial treatment. RESULTS: 54 patients (25.5%) under 70 years of age were asymptomatic at the time of diagnosis, in comparison with 25 (12.5%) of the 200 older patients (P < 0.001). Associated chronic pathologies were more frequent in the older patients (55% vs 18.5%, P < 0.001). There were no statistical differences between both groups in diagnostic delay. Localized disease was found in 127 (63%) of the younger patients and in 109 (54%) of the older patients, the difference not being significant. The percentage of patients who underwent oncological treatment was higher in the younger than the older group (87.5% vs 56%, P < 0.001). The main cause of therapeutic exclusion in both groups was poor performance status; however, in the older group other variables--such as the presence of chronic disease and patients' or relatives' wishes and doctors' opinions--influenced the decision not to give specific treatment. CONCLUSIONS: this study confirms that the clinical characteristics and treatment of aged people with cancer are different from those of younger patients. Nevertheless, there is considerable doubt about whether an arbitrary age limit should continue to be accepted as a discriminatory factor in some diagnostic and therapeutic procedures in cancer patients.

[Prognostic factors in uterine sarcomas: a 21-year retrospective study at the Clinic and Provincial Hospital of Barcelona]. / Factores pronósticos en los sarcomas uterinos: estudio retrospectivo de 21 años en el hospital Clínic i Provincial de Barcelona.

BACKGROUND: Uterine sarcomas show low incidence and poor outcome despite the treatment. The prognostic factors for the survival were determined in this study. PATIENTS AND METHODS: Thirty-nine females with sarcoma of the uterus have been studied retrospectively from January 1975 to December 1996. They were treated in the Gynecology and Radiation Oncology Departments at Hospital Clínic i Provincial of Barcelona. Thirty-seven patients had surgery, 22 radiotherapy and 4 chemotherapy. The influence on the disease-specific survival, disease-free survival, local relapse disease-free survival and metastasis disease-free survival from the following pronostic factors was studied: age, pathologic subtype, miometrial invasion, mitosis, vascular and lymphatic invasion, tumor size, stage, radiotherapy and local relapse. RESULTS: 1) The disease-specific survival at 2 and 5 years was 51.5% and 42.5% respectively, and the disease-free survival at 2 and 5 years was 39%; the incidence of local and distant relapses--was 28 and 33%. 2) The multivariate analysis showed that the overall survival and the disease free survival were affected by the vascular invasion (odds ratio [OR] 12 and 32.6, respectively) and the local failure (OR = 3 and 25.5, respectively); the only factor that affected the local relapse-free survival and metastasis free survival was the III and IV stages (OR = 5.6 in both cases). CONCLUSIONS: In uterine sarcomas, the vascular invasion and the local relapse were prognostic factors for overall survival and for disease-free survival. In stages III and IV there was a decrease in the local relapse-free survival and metastasis-free survival. A correlation between vascular invasion and advanced stages was found. The outcome of the uterine sarcomas is poor, local and distant failure being responsible for this bad prognosis.

Outcome of patients after curative resection of pulmonary metastases.

BACKGROUND: Resective surgery can play a role in solitary pulmonary metastasis or in a few multiple metastases of the lungs. METHODS: We performed a retrospective analysis of the cure rate and survival in patients with pulmonary metastases after surgical resection. Inclusion criteria included no evidence of extrapulmonary metastases or local control of the primary neoplasia. Selective adjunctive therapy was added when applicable. RESULTS: Twenty-five out of 53 patients with resected pulmonary metastases are still alive and disease free. After a 5-year period of follow-up the cure rate obtained was 42%. CONCLUSIONS: In selected patients, resective surgery of solitary or limited multiple pulmonary metastases should be useful, offering the patients a high rate of curability and long term survival. These positive results suggest that adjunctive therapies should be added after resective surgery.

Maintenance treatment with interferon alpha-2b in multiple myeloma: a prospective randomized study from PETHEMA (Program for the Study and Treatment of Hematological Malignancies, Spanish Society of Hematology).

The objectives of the present study were to investigate whether interferon alpha (IFN) maintenance could prolong response duration and survival in patients with multiple myeloma (MM) in objective response and to analyze the characteristics of relapse and subsequent survival. From January 1991 to November 1994, 92 patients from the Spanish Cooperative Group PETHEMA with MM in objective response after 12 courses of VCMP/VBAP chemotherapy were randomized to receive IFN maintenance vs no treatment until relapse. Prognostic factors at diagnosis were similar in both groups. IFN was administered at a starting dose of 3 mU/m2 three times per week. The IFN toxicity was moderate with granulocytopenia and fatigue being the most common adverse effects. Median duration of response from randomization until relapse was 13 months in the IFN group vs 7.7 months in the no treatment arm (P = 0.042). Median survival from randomization was 38.8 months for patients given IFN vs 32.7 months for those allocated to the no treatment arm (P = 0.12). Features at relapse were similar in patients who received IFN maintenance and in those assigned to no treatment. Finally, survival from relapse was identical in both groups. In summary, our results show a significant prolongation of response in patients maintained with IFN with no significant influence on survival. In addition, in our series features at relapse and subsequent outcome were similar in both groups.

p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma.

p21WAF1/Cip1 is an inhibitor of cdk/cyclin complexes, and thus regulates the cell cycle. p21 is also related to cell differentiation and is regulated by wild-type p53, although p53-independent regulatory pathways have been proposed. In order to analyse p21 expression as well as its relationship with p53 in human breast cancer, an immunohistochemical analysis was undertaken of 77 breast carcinomas, 16 of them with an in situ component; 30 adjacent normal tissue samples; and five non-neoplastic specimens. Forty-four infiltrating carcinomas (57 per cent) were p21-positive. Expression of p21 was also observed in pre-invasive lesions, whereas normal ducts were negative or focally and weakly positive. p21 expression was associated with high histological grade (II + III) (P = 0.017) and poor tubule formation (P = 0.002), and was significantly less frequent in lobular carcinomas (P = 0.0001). p21 positivity also correlated with increased proliferation, but this seemed to be dependent on the histological grade. Twenty carcinomas (26 per cent) showed p53 overexpression, but this was not associated with p21 negativity, suggesting the existence of p53-independent mechanisms for p21 regulation in vivo. Cyclin D1CCND1 expression was analysed in the same series and an association between p21 and cyclin D1 expression was found, since 23 of 26 cyclin D1-positive carcinomas were p21-positive (P < 0.001 ...). In conclusion, p21 is frequently overexpressed in breast carcinomas and this occurs in the early stages of neoplastic progression. This overexpression seems to be independent of p53 status and might be involved in cyclin D1 modulation.

Tumor markers in response monitoring and prognosis of non-small cell lung cancer: preliminary report.

BACKGROUND: The significance of tumor markers in lung cancer is not well established. PATIENTS AND METHODS: We analyzed level of serum markers as prognostic factor of response and survival in 46 evaluable patients with locally advanced or metastasic non small cell lung cancer. All patients were treated with cisplatin 120 mg/m2 or carboplatin 400 mg/m2 day 1, plus etoposide 80 mg/m2 days 1 to 3. RESULTS: Partial response was obtained in 11 patients (24%), stabilization in 18 and progression in 17. Tumor marker sensitivities were: CEA 37%, CA 125 54.5%, SCC 17.5%, NSE 30.5%, and CYFRA 52%. Higher levels of CEA and NSE correlated with more probability of response (p < 0.001 and p = 0.002). The survival probability of patients with normal pretreatment levels of NSE was significantly better than those with NSE over normal level (15.2 vs 7.2 months) p = 0.02. In patients who achieved partial response, CEA, CA 125 and CYFRA levels decreased significantly with respect to the pretreatment values. CONCLUSIONS: Patients with high CEA and NSE serum level have an increased probability of response than patients with low initial levels; however, patients with high initial level of NSE have poor survival. The decrease in CEA, CA 125 and CYFRA values at the moment of response evaluation could help in response assessment.

Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.

PURPOSE: We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS: From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS: After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION: Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.

c-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer: prognostic value.

The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of 50 healthy subjects, 58 patients with benign breast diseases, and 413 patients with breast cancer (186 locoregional, 185 with advanced disease, and 42 with no evidence of disease). Using 15 U/ml as the cut-off, no healthy subjects or patients with benign diseases and only 2.4% of no evidence of disease patients had elevated serum levels. Abnormal c-erbB-2 levels were found in 29% (101/370) of the patients with breast carcinoma (locoregional 9%, metastases 45.4%). CEA (cut-off 5 U/ml) and CA 15.3 (cut-off 35 U/ml) sensitivity was 18% and 16% in patients with locoregional disease and 61% and 70% in those patients with advanced disease, respectively. A trend toward higher serum levels of all three tumor markers in patients with nodal involvement or greater tumor size was found, but was statistically significant only with CEA (p < 0.01). By contrast, c-erbB-2 was related to steroid receptors, in both locoregional and metastatic tumors. When the prognostic value of these markers was evaluated, patients with abnormally high presurgical CEA and c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative (p < 0.05 and p < 0.001, respectively) and node-positive patients (p < 0.556 and p < 0.001, respectively). By contrast, no relationship was found between CA 15.3 values and prognosis. Multivariate analysis showed that CEA and c-erbB-2 were also prognostic factors. The correlation between serum and tissue levels of c-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p = 0.0001). Serum concentrations in patients with advanced disease were related to the site of recurrence, with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum levels seem to be a useful tumor marker in the prognosis of patients with breast cancer. Using all three tumor markers, sensitivity was 35% in patients with locoregional breast cancer and 88% in patients with recurrence.

Phase II trial of cisplatinum and etoposide in brain metastases of solid tumors.

Fourteen patients with brain metastases (BM) of solid tumors received intravenous cisplatinum, 40 mg/m2/day and etoposide, 150 mg/m2/day, for 3 days every 3 weeks. Primary tumors were lung (8 patients), breast (4), colon (1), and stomach (1). Two patients responded (1 complete response in a poorly differentiated lung cancer patient and 1 partial response in a breast cancer patient). The overall response rate was 14%, with a median survival of 6 months. Main toxicity was grade 3-4 neutropenia that occurred in 36% of patients. There were no toxic-related deaths. Chemotherapy as a single therapeutic regimen seems not to be an effective treatment for BM from relatively resistant solid tumors. Moreover, it produces rather high, although not life-threatening, hematologic toxicity.

Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status.

Cyclin D1 (CCND1) and retinoblastoma (Rb) genes are cell cycle regulators which are altered in some breast carcinomas. However, the possible cooperation between CCND1 and Rb, as well as the influence and coincidence of their abnormalities in the proliferative capacity of mammary carcinoma cells in vivo, is still unknown. In order to assess both the significance of the CCND1 gene and Rb alterations in breast carcinomas and their relationship with the proliferative capacity of the tumours and other clinico-pathological factors, CCND1 mRNA expression was studied in 46 cases of primary breast carcinomas and matched normal tissue, 45 of which were also studied immunohistochemically, Rb expression was analysed in the same cases by immunohistochemistry, whereas the proliferative activity of the carcinoma was evaluated by flow cytometry. CCND1 mRNA was overexpressed in 19 tumours (41 per cent). Sixteen cases showed diffuse immunohistochemical expression, ten carcinomas had few positive cells, and 19 were absolutely negative. CCND1 mRNA and protein overexpression was associated with oestrogen receptor (ER) expression by the tumour. Interestingly, lack of ER expression was associated with a decreased CCND1 mRNA signal in non-overexpressed tumours. No association was observed between CCND1 mRNA or protein overexpression and tumour proliferation or other clinico-pathological parameters. Loss of Rb expression was observed in 26 per cent of the tumours. This abnormality was significantly associated with increased mean S-phase (P = 0.017) and decreased CCND1 mRNA expression in non-overexpressed tumours, supporting in vivo the postulated regulatory loop between Rb and CCND1 in vitro. We conclude that CCND1 up-regulation is not associated with increased proliferative activity in breast carcinomas, whereas its expression might be regulated in vivo by hormones and Rb. Loss of Rb expression is significantly associated with an increased proliferation of tumour cells, suggesting an important role in the progression of a subset of breast carcinomas, regardless of CCND1 abnormalities.

Follow-up study in head and neck cancer: cure rate according to tumor location and stage.

The purpose of this clinical study was to analyze a long-term follow-up of all the patients with head and neck cancer in our institution. Between 1973 and 1993, 1,355 consecutive cases of head and neck cancerwere diagnosed, treated and followed up regularly. All were subjected to a multidisciplinary approach, and followed up until death or for 10 years with no event of disease. The local relapse rate was 20% and the node-regional relapse rate 15%. Distant metastases were observed in 6% of the patients mainly arising from the nasopharynx (23%) followed by the hypopharynx (11%). The main organ involved was the lung (50%). Median follow-up of the group was 10 years (range 4 months to 15 years). Cancer cure was observed after 5 years in glottic and supraglottic laryngeal carcinoma, oral and nasopharyngeal cancer and after 2.5 years in patients with cancer of the oropharynx and hypopharynx. The highest cure rate was 80% in the glottis, followed by 70% in the supraglottic area, 45% in the mouth, 30% in the nasopharynx, 25% in the oropharynx, and 20% in the hypopharynx. A second primary tumor was observed in 7% of the patients and a third primary in 0.6% of the patients. Only in 7 patients, the second or third primary was seen after 5 years of follow-up. Curability should be observed after 5 years from definitive therapy of glottic, supraglottic, oral and nasopharyngeal and earlier in oropharyngeal and hypopharyngeal cancer. Further follow-up should be discontinued. Second and third neoplasias are the main problems after 5 years of follow-up but their incidence is low.

CHOP vs. ProMACE-CytaBOM in the treatment of aggressive non-Hodgkin's lymphomas: long-term results of a multicenter randomized trial.(PETHEMA: Spanish Cooperative Group for the Study of Hematological Malignancies Treatment, Spanish Society of Hematology).

From May 1985 to May 1989, 175 patients with previously untreated aggressive non-Hodgkin's lymphoma were randomized to receive CHOP or ProMACE-CytaBOM. Eligibility criteria included follicular large-cell diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic lymphoma with an Ann Arbor stage II, III or IV. One hundred and forty-eight patients were evaluable. There were no significant differences between the 2 treatments in response rate (83.5% [57.5% CR] for CHOP vs. 88% [62% CR] for ProMACE-CytaBOM), time to treatment failure (29% vs. 31% at 5 yr), or overall survival (42% in both groups at 5 yr). Furthermore, there were no significant differences between the 2 regimens when response rates and outcome were analyzed for different prognostic subgroups. Toxicity was not significantly different between the 2 regimens, although only 1 patient died as result of treatment-related toxicity in the CHOP arm compared to 6 patient in the ProMACE-CytaBOM group (p = 0.126). In conclusion, in this study ProMACE-CytaBOM has not proved to be superior to CHOP in aggressive lymphomas. This trial gives support to the notion that CHOP still is the standard chemotherapy for aggressive lymphomas, and that new treatment approaches for these lymphomas should be compared to CHOP.

Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3.

To evaluate the utility of c-erbB-2, carcinoembryonic antigen (CEA) and CA 15.3 in the early diagnosis of recurrence, serial serum determinations of these antigens were performed in 200 patients (follow-up 1-4 years, mean 2.2 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Eighty-nine patients developed metastases during follow-up. C-erbB-2, CEA and CA 15.3 were elevated (> 20 U ml-1, > 10 ng ml-1 or > 60 U ml-1 respectively) before diagnosis in 28%, 30% and 47% of the 89 patients with recurrence, with a lead time of 4.5 +/- 2.4, 4.9 +/- 2.4 and 4.8 +/- 2.4 months respectively. Tumour marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver metastases. When patients with locoregional recurrences were excluded, sensitivity improved: 31% (c-erbB-2), 33% (CEA) and 56% (CA 15.3), with 76% having at least one of the three tumour markers. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (8/10, 80%) than in those without overexpression (1/30, 3.3%) (P = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PR+ patients (CA 15.3, P < 0.0001) or in PR- patients (c-erbB-2, P = 0.009). Specificity of the tumour markers was 100% for all three markers (111 NED patients). In conclusion, c-erbB-2 is a useful tool for early diagnosis of metastases, mainly in those patients with c-erbB-2 overexpression in tissue. Using all three markers simultaneously it is possible to increase the sensitivity in the early diagnosis of recurrence by 11.2%.

Treatment of multiple myeloma in elderly people: long-term results in 178 patients.

The purposes of the present study have been to analyse the presenting features, response to therapy and survival of myeloma patients aged 70 years or more, in comparison to younger patients. From January 1985 to December 1989, 487 patients with multiple myeloma (MM) were randomized to receive melphalan and prednisone (MP) versus alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, BCNU, adriamycin, and prednisone (VBAP). The subset of 178 patients who were 70 or more years is the subject of this study, whereas the 309 patients younger than 70 years were used as a control group. The presenting features and response to chemotherapy of older patients were no different to those of the younger population. However, the survival of elderly patients was significantly shorter (median 23.4 vs. 33.5 months, p < 0.001). The overall response rate to MP in older patients was 50% (28% objective plus 22% partial response) compared with 61% (44% objective plus 17% partial response) to combination chemotherapy (p = not significant). Myelosuppression was moderate in both arms, although MP produced a higher degree of thrombocytopenia. There were no significant differences in survival between patients given MP versus VCMP/ VBAP (median, 20 vs. 27 months, p = 0.2). Response to treatment was associated with a significantly longer survival. Older patients with symptomatic myeloma tolerate chemotherapy and should be offered treatment.