Monoclonal antibodies and synthetic tumor-associated glycoconjugates in the study of the expression of Thomsen-Friedenreich-like and Tn-like antigens on human cancers.

Synthetic carbohydrate haptens, which are conjugated to carrier human serum albumin molecules [synthetic tumor-associated glycoconjugates (S-TAGs)], were used to immunize mice for monoclonal antibody (MoAb) production. Two of the S-TAGs were composed of haptens related to the Thomsen-Friedenreich (TF) antigen, and their structures are beta Gal(1----3)-beta GalNAc (TF-beta) and beta Gal(1----3) alpha GalNAc (TF-alpha) (Gal = galactose; GaNAc = N-acetylgalactosamine). The third S-TAG was made up of Tn hapten groups of the structure alpha GalNAc-O-serine. MoAbs specific for TF-alpha and Tn were able to be generated. All MoAbs generated against TF-beta cross-reacted with TF-alpha but not with Tn. None of the TF-alpha-specific MoAbs reacted with human carcinomas, whereas several TF-beta and Tn MoAbs were found to react with most human lung, colon, and breast carcinomas. It is believed that this is the first report of the use of synthetic carbohydrate cancer antigens for the production of anticancer MoAbs.

Antigenic heterogeneity of human colorectal cancer cell lines analyzed by a panel of monoclonal antibodies. I. Heterogeneous expression of Ia-like and HLA-like antigenic determinants.

The pattern of reactivity of 10 monoclonal antibodies (MCA) developed against human lymphoid leukemia cells and tested with human T-cells, B-cells, as well T-lymphoma and B-lymphoma cell lines suggested that six of them detect la-like determinants, three detect HLA-like determinants, and the remaining one detects a non-Ia B-cell antigen. With the use of three binding assays, the six MCA that appeared to detect Ia-like determinants reacted strongly with the human colorectal cancer cell (CCC) line LoVo, and none of the three MCA that reacted with HLA-like determinants reacted with this cell line. Immunoprecipitation and polyacrylamide gel electrophoresis analysis confirmed the apparent specificities of the MCA for Ia-like and HLA molecules, demonstrated the presence of Ia-like molecules in LoVo, and failed to detect HLA in these cells. The cellular enzyme-linked immunosorbent assay was used for the testing of our anti-Ia and anti-HLA MCA with 15 other CCC lines. Marked heterogeneity was found in the expression of different Ia-like and HLA determinants defined by different or overlapping subsets of MCA, which suggested that these determinants might be present on different molecules or that different conformations of the same molecules exist in various CCC lines. Analysis of the surface phenotype of subclones of LoVo cells revealed the presence of stable variant cell subpopulations, which lost reactivity with four out of six of the anti-Ia-like MCA but retained at least one Ia-like molecule recognized by two of our MCA. All of the subclones maintained the HLA-negative phenotype. The possible immunologic and diagnostic consequences of the presence or absence of Ia-like or HLA markers on nonlymphoid tumor cells are discussed.

Analysis of human tumor associated Thomsen-Friedenreich antigen.

The Thomsen-Friedenrich (TF) antigen is a precursor structure of MN blood group antigens and is also expressed by about 90% of human carcinomas. The immunodominant group of TF antigen [beta-galactosyl(1-3)-alpha-N-acetylglactosamine] is present in cryptic form in normal RBC and is revealed by neuraminidase treatment. A murine monoclonal antibody (Mab 49H.8) developed against neuraminidase treated human RBC was reactive against a variety of human tumors. We have characterized the human tumor associated TF antigen detected by this antibody from a human transitional bladder carcinoma cell line (647V), a human colon adenocarcinoma cell line (LS174T), and a pleural effusion fluid of a breast adenocarcinoma patient (PE 89). A heterologous sandwich radioimmunoassay for TF antigen was developed using Mab 49H.8 as the catcher and 125I-peanut agglutinin as the probe. Detergent extracts of 647V and LS174T cells, media conditioned by culturing these cells, and PE 89 were shown to contain the antigen by this assay. The specificity of the antigen capture by Mab 49H.8 in this assay was demonstrated by its selective inhibition by nitrophenyl-beta-D-galactoside, phenyl-beta-D-galactoside, and a TF hapten. Preliminary studies on TF antigen in serum samples using this assay showed that about 53.7% of the carcinoma samples contained an antigen concentration greater than 200 units/ml whereas for 90.9% of the normal samples the antigen concentration was below 200 units/ml. These studies demonstrated that the TF antigen is shed by the tumor cells both in vitro and in vivo. The TF antigen was sensitive to treatment with alkali (0.1 M NaOH for 5 h at 37 degrees C) and periodate (10 mM sodium periodate for 1 h at room temperature), was resistant to acidic pH (50 mM acetate buffer, pH 4.5, for 5 h at 37 degrees C), and could be extracted with perchloric acid (0.6 M for 1 h at 4 degrees C). The antigen was shown to be a high molecular weight glycoprotein (Mr greater than 1,000,000) by gel filtration chromatography. The density of the antigen was estimated to be about 1.35 g/ml by cesium chloride density gradient centrifugation. The antigen could be isolated from conditioned media by a combination of affinity chromatography and gel filtration with an overall purification of about 61,432-fold and a final recovery of 53.2%.(ABSTRACT TRUNCATED AT 400 WORDS)

Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen.

In a phase I study, ten ovarian cancer patients with extensive metastatic disease despite chemotherapy were immunized three to eight times subcutaneously with the synthetic form of the immunodominant disaccharide (beta Gal1----3 alpha GalNAc) of the Thomsen-Friedenreich antigen conjugated to KLH (TF alpha-KLH) plus DETOX adjuvant. Six patients were given a "low" dose of TF alpha-KLH (100 micrograms/injection) and four patients were given a "high" dose (500 micrograms/injection). All patients received a single low-dose cyclophosphamide treatment (200 mg/m2 i.v.) 3 days prior to commencement of the series of immunizations. Immunizations were 2 weeks apart. Little or no toxicity was noted. As expected, all patients (prior to immunization) had naturally occurring IgM antibodies against the synthetic TF alpha hapten. None of the patients had detectable pre-existing IgG or IgA antibodies against synthetic TF alpha hapten. Nine of the ten ovarian cancer patients showed a significant increase in IgM titer above pre-existing levels following immunizations with TF alpha-KLH plus DETOX adjuvant. These same patients also produced IgG anti-TF alpha and eight of these also produced IgA anti-TF alpha, although the IgA responses were weaker. Most of the IgG responses followed the IgM responses by 2-4 weeks. Two patients produced a vigorous IgG response after their first TF alpha-KLH injection, suggesting a recall response. Both direct ELISAs on various solid-phase synthetic carbohydrate antigens and hapten inhibition experiments confirmed the TF alpha hapten specificity of the antibodies. IgM and IgG anti-TF alpha-specific antibodies reacted with natural TF antigen, by ELISA and FACS analysis, although the titers were generally lower than the titers against the immunizing TF alpha hapten. Increased levels of cytotoxic antibodies against TF-expressing tumor cell targets were detected in eight of the ten patients following immunization. One patient who had no detectable cytotoxic antibodies prior to immunization developed increasingly strong cytotoxic antibodies as a function of the number of immunizations. The low antigen dose patients showed as good or better humoral immune responses than the high antigen dose patients. All four high-dose and four of six low-dose patients developed moderate to strong DTH reactions at the vaccination sites. Our results demonstrate that KLH is an acceptable carrier for carbohydrate haptens in humans and that DETOX is an appropriate nontoxic adjuvant for the generation of high-titer specific anti-carbohydrate responses in human cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical outcome of breast and ovarian cancer patients treated with high-dose chemotherapy, autologous stem cell rescue and THERATOPE STn-KLH cancer vaccine.

The purpose of this study was to evaluate the toxicity and potential efficacy of administering the THERATOPE STn-KLH cancer vaccine to ovarian and breast cancer patients after an autologous stem cell transplant. Forty patients (11 high-risk stage II/III breast cancer, 22 stage IV breast cancer, and seven stage III/IV ovarian cancer patients) were treated with high-dose chemotherapy followed by autologous/syngeneic stem cell rescue and vaccination with THERATOPE STn-KLH (Sialyl-Tn-KLH with Detox-B Stable Emulsion). Each patient was scheduled to receive a total of five vaccinations beginning on days 30-151 after stem cell infusion. The vaccine was well tolerated. Induration and erythema at the site of injection were the most common side-effects. When one compares the outcome of patients vaccinated with 66 breast and ovarian cancer patients who were not, following risk-adjustment analysis, vaccinated patients appeared more likely to survive (P = 0.07) and less likely to relapse (P = 0. 10). Vaccinated patients with the greatest specific lytic activity against STn+OVCAR tumor cells relative to nonspecific killing of Daudi cells tended to remain in remission longer than patients who displayed less specific immune activity (P = 0.057). We conclude that the THERATOPE STn-KLH cancer vaccine is well tolerated in breast and ovarian cancer patients after autologous transplant and, while not statistically significant, the trends in data support the concept that THERATOPE vaccine may decrease the risk for relapse and death and thus warrants further study. Bone Marrow Transplantation (2000) 25, 1233-1241.

Immune responses of mice and human breast cancer patients following immunization with synthetic sialyl-Tn conjugated to KLH plus detox adjuvant.

We generated a synthetic epitope, NANA alpha(2-6) GalNAc alpha-O-Crotyl (STn-crotyl), designed to "mimic" the natural O-linked epitope expressed on human carcinoma cells, NANA alpha(2-6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm, and a "vaccine" containing STn-KLH plus DETOX adjuvant was formulated. The immunogenicity of the vaccine was evaluated preclinically in CAF1 mice and subsequently in patients with metastatic breast cancer. The specificity and titers of IgG antibodies were evaluated by kinetic ELISA on synthetic STn-HSA and on ovine submaxillary mucin (OSM) solid phases. Ovine submaxillary mucin is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 micrograms of STn-KLH produced IgG titers ranging from 1:10(4) to 1:10(5) when tested on solid phase OSM. Anti-OSM IgG, both polyclonal and monoclonal antibodies, generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. These monoclonal antibodies also bound to STn determinants on human tumor cell surfaces. Breast cancer patients immunized with 100 micrograms of the same vaccine produced median peak IgG titers 1:1280 measured on STn-HSA and 1:160 on OSM. Hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little evidence that the artificial linker arm (crotyl linker) contributed substantially to either the titer or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha(2-->6)-GalNAc. Small but not large doses of STn-KLH immunogen induced anti-STn DTH responses in mice that were inversely proportional to the antibody responses. Evidence of a clinical response was noted in some of the immunized breast cancer patients, with other patients showing prolonged disease stability.

Possible utility of serum determinations of CA 125 and CA 27.29 in breast cancer management.

The utility of measurement of serum levels of the tumor associated antigens CA 125 and CA 27.29 in detecting the presence of disease and in monitoring changes in disease status was examined in 63 patients with breast cancer. In patients with clinically detectable disease the CA 125 level was elevated in 59%, the CA 27.29 level in 59.5% and one or both markers in 84.6%. Specificity for presence of disease was 83.6% for CA 125, 88% for CA 27.29, and 69.1% for the two markers combined. Changes in marker levels of more than 50% correlated with clinical changes in disease status in 58% of cases for either CA 125 or CA 27.29 alone. In 87.5% of cases with clinically progressive disease one or both marker levels increased by more than 50% from the previous levels. In no case with greater than 50% increase in a marker level was there regression of disease. Thus, the use of these markers in combination might have utility in cases where diagnosis of recurrent disease is difficult or where monitoring of response to treatment is hampered by lack of measurable disease.

Clinical evaluation of a new two-site assay for CA125 antigen.

As appropriate surgery and chemotherapy can improve both quality of life and survival of patients with ovarian adenocarcinoma, there has been a pressing need for "serodiagnostic" assays to enable close patient monitoring. CA 125 antigen has previously been described as a useful tumor marker of ovarian cancer. This is the first clinical evaluation of a radioimmunoassay using two new monoclonal antibodies, B27.1 and B43.13, that react with separate sites on the glycoprotein marker CA 125. Using the new assay, the majority of patients with clinically or radiologically detectable disease had serum CA 125 antigen levels well above the upper limit seen with random apparently healthy donors, while only three patients who were believed free of disease had elevated levels. Disease progression was associated with increasing values of serum CA 125 antigen, while response to therapy was associated with a steady decline in serum CA 125 antigen levels. Seven patients had steadily rising serum CA 125 antigen levels after initially having normal levels. The mean lead time between rise above normal and clinical or radiological evidence of relapse was 5 months (range 2 to 12 months). The merits of further surgical intervention are illustrated by the serial values of two patients followed after chemotherapy. The assay appears to have value in monitoring response to therapy and in detecting disease relapse at a time when appropriate therapeutic intervention is still possible or likely to be beneficial. Furthermore, monitoring CA 125 antigen was shown to be of benefit in assessing response to chemotherapy in a few patients with metastatic adenocarcinoma of unknown primary, and may be useful in this group of patients in determining those likely to benefit from aggressive chemotherapy.

A phase I/II study combining radical radiotherapy with concurrent cisplatin in the treatment of advanced squamous cell carcinoma of the cervix.

Sixteen patients with advanced cervix cancer have been treated in a phase I/II study of concurrent radiotherapy and cisplatin chemotherapy. The external beam radiotherapy was given as a 'split course' because of initial concerns about acute toxicity. The treatment was well tolerated with all patients completing the prescribed radiotherapy and all patients received the intended four doses of cisplatin. One of 5 patients with stage IVB disease is alive and disease free 35 months after treatment. Six of the 11 patients with disease confined to the pelvis are alive and disease free between 28 and 53 months after treatment. One patient has required surgery for a recto-sigmoid stricture.

The effects of circulating antigen on the pharmacokinetics and radioimmunoscintigraphic properties of 99m Tc labelled monoclonal antibodies in cancer patients.

UNLABELLED: PURPOSE. This article reports the pharmacokinetics, radiation dosimetry and radioimmunoscintigraphy (RIS) of two (99m)Tc-labelled monoclonal antibodies (MAb) used to detect cancer. METHODS: The effects of circulating antigen in female cancer patients are explored and their effects on the ability of these MAbs to effectively perform as RIS agents noted. To illustrate the effects of circulating antigen, data using MAb B43.13 (OVAREX, AltaRex Corp., Waltham, MA, USA) from a Pilot study in ovarian cancer patients are presented. The results from a Phase II study of MAb 170H.82 (Tru-Scint AD, BIOMIRA INC., Edmonton, Alberta, Canada) in patients with primary and locally recurrent breast cancer were used to portray the biodistribution patterns when no circulating antigen is present. Data from planar gamma camera images were obtained for both groups and used for pharmacokinetic and radiation dosimetry analyses. RESULTS: A pharmacokinetic analysis indicated a shorter residence time and higher clearance of (99m)Tc-MAb-B43.13 that was ascribed in part to the circulating CA 125 antigen in this group of ovarian cancer patients. CONCLUSION: These clearance patterns resulted in acceptable, though higher radiation doses to the spleen and urinary bladder wall for these patients when compared to the MAb-170H.82 group. Both MAbs were found to produce acceptable radioimmunoscintigraphic images

MAb 170H.82: an evaluation of a novel panadenocarcinoma monoclonal antibody labelled with 99Tcm and with 111In.

A novel method for generating monoclonal antibodies against synthetic tumour-associated glycoconjugates has been developed. One of these monoclonal antibodies, designated 170H.82, was derived against the TF antigen and has been shown in vitro to have a wide range of reactivity with adenocarcinoma. This antibody has been labelled with 111In and 99Tcm and has been evaluated in pilot clinical trials involving 48 patients with a range of adenocarcinoma. Overall clinical accuracy with the radiolabelled antibody was 92%, with the antibody appearing to have particular clinical utility in gynaecological and breast cancers. Single photon emission computed tomographic (SPECT) imaging was shown to improve the quality of the images and to improve the diagnostic sensitivity. We believe that this unique antibody, labelled with 99Tcm, appears to offer promise for routine clinical use in the evaluation of patients with a range of primary and metastatic adenocarcinoma.

Specificity of the IgG response in mice and human breast cancer patients following immunization against synthetic sialyl-Tn, an epitope with possible functional significance in metastasis.

Several investigators have shown that the expression of the sialyl-Tn (STn) epitope on cancer associated mucins is associated with a poor prognosis in several human cancers suggesting that STn may have functional significance in metastasis. We postulate that antibodies against the STn-epitope can inhibit metastasis. We generated a synthetic "mimic", NANA alpha (2-->6)GalNAc alpha-O-Crotyl (STn-crotyl), of the natural O-linked epitope on mucins, NANA alpha (2-->6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm and a "vaccine" containing STn-KLH plus Detox adjuvant was formulated. The immunogenicity of the vaccine was evaluated in BALB/c mice and in metastatic breast cancer patients. The specificity and titres of IgG antibodies were evaluated by ELISA on ovine submaxillary mucin (OSM) solid phases. OSM is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 microgram of STn-KLH produced a median IgG titre of over 1:5000 on solid phase OSM. Anti-OSM IgG monoclonal antibodies generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. Breast cancer patients immunized 2-8 times with 25 or 100 micrograms of the same vaccine produced median peak IgG titres 1:1280 measured on STn-HSA and 1:80 on OSM. Once again, hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little or no evidence that the artificial linker arm (crotyl linker) contributed significantly to either the titre or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha (2-->6)GalNAc. Evidence of a clinical response was noted in several of the immunized breast cancer patients with other patients showing prolonged disease stability.

Developing a midwifery workload management system: a preliminary report.

Individualised care, quality assurance and resource management are words frequently on the lips of midwives today. This paper describes a project currently being undertaken in West Glamorgan Health Authority where these criteria each form an important part of the study. It is in considering these varying aspects concurrently that the authors claim a unique approach. Resources are only considered to be managed appropriately when client centred quality care is provided. As an additional benefit, the review of policy and practice and an evaluation of the implementation of the 'midwifery process' form an integral part of the study.

A preliminary evaluation of education material prepared for the Safe Motherhood Initiative Educational Project.

Maternal death is a tragedy which is all too familiar in much of the world. As part of the Safe Motherhood Initiative the World Health Organization is developing and producing a learning package designed specifically for midwives. Through a modular system of learning incorporating aspects of community, prevention, treatment and follow-up the package seeks to address the five main causes of maternal mortality. In this paper the first pre-testing of the educational material in an African country is described. The extent of the evaluation is limited at this early stage but the initial analysis of the results is encouraging and have led to modifications of the original package. The evaluation has confirmed that a tool such as this package can be a valuable resource for midwife teachers attempting to improve the relevance of education for their midwifery students. The midwifery students whilst being 'with woman' in childbirth are also grappling with the realities of death in their everyday practice. The educational package has also reinforced the sense of urgency fundamental to completing this extensive project so that it can be made available to midwives throughout the developing world at the earliest opportunity.

Clinical significance of the Thomsen-Friedenreich antigen.

What is the clinical significance of the expression by common human carcinomas of the Thomsen-Friedenreich (TF) antigen? Described as a terminal disaccharide which is a precursor of MN blood group antigens, it was discovered as a laboratory curiosity 60 years ago, yet its cancer-association has only been appreciated in the last two decades. It is cryptic in the membrane of various normal cells, but can be found overtly expressed early during malignant transformation. It thus has potential as a target antigen for monoclonal antibodies for the detection of cancers, both in vitro and in vivo. Several studies have described its expression in relation to tumor grade, metastasis and likelihood of relapse or tumor aggression, and attempts have been made to define its prognostic significance, but generalization is difficult because of differing trends in expression on different types of cancers. TF is immunogenic, and perhaps even immunomodulatory in patients with cancer. We have used natural and synthetic TF and related antigens to study this immunomodulation in an animal model. Natural TF can be either immunogenic or immunosuppressive. In an appropriate formulation synthetic TF can be used in an 'immunotherapeutic vaccine' to significantly prolong the lives of animals which have an otherwise lethal mammary cancer. We are now testing similar immunotherapeutic vaccines in humans with cancer, and have induced an immune response to synthetic TF, the same serum also reacting with cancer cells known to express TF. The clinical significance of TF may be the immune response it induces, either tolerizing a patient to a cancer or stimulating an effector response to a cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

New possibilities for cancer therapy with advances in cancer immunology.

There has been progress over the last decade in addressing three questions: Are there cancer-associated antigens that could be targets for immunotherapy? Can the human immune system recognize cancer-associated antigens? Can an anti-cancer immune response affect cancer cells and lead to increased survival? Results from animal model studies have been interpreted by optimists as encouraging, and by pessimists as being irrelevant to human cancer. Earlier studies on "cancer vaccines" utilized heterogeneous cell extracts of cell components. Monoclonal antibodies have enabled identification of relevant cancer-associated antigens or epitopes, such as the ganglioside GM2, the carbohydrates TF and STn, and the peptide sequences of MUC-1. In parallel with research on immune adjuvants and measures designed to inhibit suppressor activity, these epitopes are being tested for their potential in the immunotherapy of solid tumors. It is clear that some of these cancer-associated epitopes are immunogenic in humans. Mixed responses may relate to cancer heterogeneity and may indicate the importance of multi-epitopic vaccines. Responses are encouraging, but are they relevant? Prolonged disease stability challenges us to re-think the goals of cancer therapy. Recent advances in the knowledge of the effect of cytokines on tumor antigen expression and the regulation of the immune response, coupled with advances in active specific immunotherapy, provide hope that biomodulation may become an important part of the therapy of solid tumors in the next century.

The serum prolactin level in testicular tumours--a new tumour marker?

Serum prolactin levels were elevated above the range seen in normal male subjects of 7 of 11 patients with non-seminomatous testicular tumours, particularly in patients with metastatic disease. In contrast, the mean prolactin level in patients with seminomas was not significantly different from normal, and only one of eight patients had a serum prolactin concentration beyond the normal range. In two subjects with non-seminomatous testicular tumours serial measurements of prolactin and chorionic gonadotrophin showed a striking parallelism and accurately predicted clinical progress. Serum prolactin may be a useful additional tumour marker in patients with non-seminomatous testicular tumours.

Prognostic significance of preimmunotherapy serum CA27.29 (MUC-1) mucin level after active specific immunotherapy of metastatic adenocarcinoma patients.

The TRUQUANT BR radioimmunoassay, which uses monoclonal antibody B27.29 to quantitate CA27.29 mucin antigen (MUC-1 gene product) in serum, has recently received Food and Drug Administration approval for predicting recurrent breast cancer in patients with stage II and III disease. The purpose of this study was to determine whether the new radioimmunoassay for serum MUC-1 has prognostic significance for patients with metastatic adenocarcinoma receiving active specific immunotherapy (ASI). Using 40 U/ml as the upper limit of "normal," patients with metastatic breast and ovarian cancer with a preimmunotherapy serum CA27.29 mucin > 40 U/ml (CA27.29 Hi patients) had a poorer survival than CA27.29 Lo patients (< or = 40 U/ml) after ASI. There was no significant correlation between preimmunotherapy CA27.29 serum levels and measurable tumor burden. The preimmunotherapy CA27.29 serum level was a predictor of poor survival of metastatic colorectal and pancreatic cancer patients independent of other prognostic factors. There seemed to be two populations of pancreatic cancer patients, separated at 60 U/ml serum CA27.29 (CA27.29 Hi versus Lo patients). A CA27.29 serum level of 22 U/ml separated patients with CA27.29 Hi vs. Lo colorectal cancer. Patients with CA27.29 Lo colorectal and pancreatic cancer survived longer after ASI compared with patients with CA27.29 Hi colorectal and pancreatic cancer, respectively. We suggest that various CA27.29 serum levels define poor prognosis patients (CA27.29 Hi secretors) versus good prognosis patients (CA27.29 Lo secretors) for different cancer types.

The treatment of advanced recurrent carcinoma of the uterine cervix with platinum based cytotoxic chemotherapy.

Nineteen patients with advanced recurrent carcinoma of the uterine cervix received platinum based chemotherapy between February 1982 and April 1984. All patients had received prior pelvic irradiation. Eleven patients received combination chemotherapy with platinum, vinblastine and bleomycin (PVB), and 8 patients received a regimen of platinum and 5-fluorouracil (PF). Two patients achieved a complete response and 4 patients achieved a partial response, a total response rate of 33%. Five out of 6 responders received PVB. The median survival (MS) was 8 months (1-38) months from the first treatment with cytotoxic chemotherapy. In those patients achieving a response, MS was 13.5 months (6-38+ months) with 1 patient alive at 38 months, compared to an MS of 5 months (1-15 months) in those patients without response. Toxicity was significant with nausea and vomiting in the majority of patients. Two patients refused treatment after the first course because of toxicity. The morbidity of treatment was such that despite an encouraging response rate, particularly to PVB (45%), the routine use of such treatment must be questioned.