The usefulness of CA15.3, mucin-like carcinoma-associated antigen and carcinoembryonic antigen in determining the clinical course in patients with metastatic breast cancer.

Levels of mucin-like carcinoma-associated antigen (MCA), CA15.3 and carcinoembryonic antigen (CEA) were measured in consecutive serum samples of 40 women with metastatic breast cancer. A change in antigen level of more than 25%, either an increase or a decrease, was considered to predict progressive or responsive disease respectively. A change of less than 25% was considered to predict stable disease. MCA, CA15.3 and CEA were elevated in the serum of 68%, 76% and 48% of the patients respectively (P < 0.05). The overall prediction of clinical course was similar for all three markers. A more than 25% increase of MCA, CA15.3, and CEA was observed in 61%, 54% and 36% respectively. The predictive value of a more than 25% increase was high for all three markers: 94%, 94%, 83%. Changes in marker levels were correlated with each other. Logistic regression analysis showed that combining MCA and CA15.3 did not improve the prediction further. In conclusion, these tumour markers may help in evaluating the disease course and there is no advantage in combining MCA and CA15.3.

Palliative radiation therapy for AIDS-associated Kaposi's sarcoma by using a single fraction of 800 cGy.

A single radiation fraction of 800 cGy was used in the treatment of acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). A total of 74 radiation treatments was given to a total of 31 patients. Of all 74 evaluable treatments, there were 25 objective major responses (6 complete, 19 partial) according to the WHO criteria, while 67 treatments resulted in subjective palliation of the main reason to treat (cosmetic discomfort, pain, or oedema). However, it appeared that the duration of these responses was rather short; in 23 of 36 radiation treatments with a follow-up of more than 4 months, progression of the tumour was seen within that time, while the palliative effect outlasted the survival of the patients in only four cases. It is concluded that a single dose of 800 cGy is an effective treatment for patients with a predicted survival of only a few months, and it should be determined whether a higher fractionated dose improves duration of responses, especially for patients with a good performance.

Low incidence of anti-interferon-alpha antibodies in patients treated with interferon-alpha-2a for AIDS-associated Kaposi's sarcoma.

Anti-interferon (IFN)-alpha antibodies were determined in the serum of 28 patients treated with high-dose human recombinant IFN-alpha-2a for AIDS-associated Kaposi's sarcoma. After a median treatment duration of 3 months, 3 patients developed anti-IFN-alpha antibodies, of whom 2 showed a long lasting tumour response despite the development of these antibodies. None of 3 patients with tumour progression after an initial treatment response had developed IFN-alpha neutralizing antibodies. In conclusion, a low incidence of anti-IFN-alpha antibodies during treatment with high dose IFN-alpha was found, but the appearance had no detrimental effect on the duration of tumour responses in a small number of patients.

Temporary increase in serum beta 2-microglobulin during treatment with interferon-alpha for AIDS-associated Kaposi's sarcoma.

Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment. However, the increase of serum beta 2-M levels in responders appeared to be more pronounced than in those with progressive disease, but this difference was not significant. The increase was only found during the initial 8 weeks; thereafter, beta 2-M levels declined in patients with continuing clinical improvement during ongoing treatment with IFN alpha. This may have been related to IFN alpha dose modification at 8 weeks for all patients. The initial rise in serum beta 2-M might be related to the immunomodulation properties of IFN alpha. Because serum beta 2-M levels were also enhanced in non-responders, this rise does not demonstrate that immunomodulation by IFN alpha is a mechanism of anti-tumour activity in AIDS-associated Kaposi's sarcoma.

Lack of activity of zidovudine in AIDS-associated Kaposi's sarcoma.

The efficacy of zidovudine (AZT) for treatment of patients with Kaposi's sarcoma as the initial manifestation of AIDS was determined in a non-randomized, phase-II clinical trial. Twenty-two patients were treated with zidovudine (300 mg 4 times daily for 8 weeks). In patients with stable disease or showing a response, treatment was continued. After 12 weeks the total daily dose was changed to 1000 mg. Only two of all 22 evaluable patients achieved a response (one complete and one partial response), of only brief duration (2 and 4 months, respectively). There was no such association between antiretroviral activity, increase in CD4+ cells and tumour response, as was reported during treatment with human recombinant interferon alpha (IFN-alpha). These findings do not support the use of zidovudine as a first-line treatment for patients with AIDS-associated Kaposi's sarcoma.

Phase II study of recombinant interferon alpha-2a and vinblastine in advanced renal cell carcinoma.

A total of 66 patients with advanced renal cell cancer received a combination of recombinant interferon alpha-2a (18 times 10(6) units subcutaneously 3 times weekly) and vinblastine (0.1 mg. per kg. intravenously every 3 weeks). Four patients were ineligible and 6 were inevaluable for response but evaluable for toxicity. There were no complete and 9 partial responses among the 56 evaluable patients, for a response rate of 16 per cent. Median duration of response was 26 weeks, with a range of 8 to 50 weeks. Responses were observed predominantly in patients with lung and soft tissue metastases. Patients who had undergone nephrectomy did not show a better response rate than those who had not. Almost all patients had a flu-like syndrome, fatigue and anorexia. Other side effects included leukopenia, nausea, vomiting, liver function disturbances and neurotoxicity. Most of the side effects were World Health Organization grade 1 or 2; no grade 4 toxicity was observed. Antibodies against interferon developed in 6 patients during the course of treatment. However, there was no relationship between the appearance of antibodies and disease progression. The combination of recombinant interferon alpha-2a and vinblastine has modest but definite activity in patients with advanced renal cell carcinoma, although the role of vinblastine is unclear.

Clinical and virological effects of high-dose recombinant interferon-alpha in disseminated AIDS-related Kaposi's sarcoma.

The effectiveness and antiretroviral activities of interferon-alpha in AIDS-related Kaposi's sarcoma was assessed in a non-randomised, phase-II clinical trial. 28 patients were treated with high-dose (27-36 MU) human recombinant interferon-alpha 2a subcutaneously every day for 8 weeks. In patients with stable disease or showing a response, treatment was continued three times weekly until a complete response was achieved or there was progression. 12 of the 26 evaluable patients achieved a major response; 5 of these showed histologically confirmed complete responses. There was a significant increase in OKT4-positive cells in the responders and a significant decrease in HIV antigen (HIV-Ag) in the 7 responders with initially detectable HIV-Ag. Interferon-alpha is thus an effective treatment. The increase in OKT4-positive cells and the decrease in HIV-Ag seem to be significantly related to patients with tumour responses.

Etoposide for epidemic Kaposi's sarcoma: a phase II study.

Fourteen untreated patients with epidemic Kaposi's sarcoma stages III and IV were treated with etoposide 150 mg/m2 on 3 consecutive days every 4 weeks. No responses were observed. Myelosuppression was severe with white blood count WHO grade 3-4 in nine patients and with platelets WHO grade 3-4 in one patient. Three patients developed opportunistic infections during therapy. It is concluded that etoposide is inactive in epidemic Kaposi's sarcoma.

Increased plasminogen activator inhibition levels in malignancy.

Plasminogen activator(PA)-tissue and urokinase type-and PA-inhibition in plasma were investigated in 52 consecutive cancer patients with a variety of tumors. At first patients were analyzed as one group. Secondly patients were subdivided into two groups, one with (n = 42) and one without (n = 10) metastasis. Our results show that tissue-type-PA antigen (t-PA-antigen) and PA-inhibition were both significantly increased irrespective of the presence or absence of tumor metastasis (p less than 0.001 compared to age matched healthy controls. In the group without metastasis a significantly decreased level of t-PA activity was found (p less than 0.001) but in the group with metastasis t-PA activity was normal. These data seem to reject the hypothesis that decreased plasma fibrinolytic activity is one of the prerequisites for tumor metastasis.