Prospective comparison of intralesional and multipuncture BCG in recurrent intradermal melanoma.

Fifty-nine patients with metastatic melanoma predominantly localized in the skin were randomly assigned to treatment with BCG given either intralesionally (IL-BCG) or by multiple puncture vaccination at a nontumor bearing site in the skin (MPV-BCG). Half the patients with IL-BCG experienced moderate fever, chills and malaise, suggesting systemic exposure to this live organism. However, only three of these patients required systemic antituberculous chemotherapy and all responded to it. MPV-BCG treated patients experienced significantly less systemic toxicity. Among fully evaluable patients 45% objective response rate was seen in the IL-BCG group and a 9% response rate in the MPV-BCG group, a significant difference. The only complete responses were seen in the IL-BCG group. Among fully evaluable patients, median survival was 21.1 months in the IL-BCG group and 13.3 months in the MPV-BCG groups (NSD). No patients with pretreatment anergy to all skin tests utilized, experienced objective response to BCG.     

Nonfamilial Turcot's syndrome associated with Turner's syndrome, multiple carcinomas of the tongue, and cancer of the colon

Herein we present the clinical and cytogenetic data of a patient with Turner's and Turcot's syndrome associated with multiple carcinomas of the tongue and cancer of the colon.     

Subcutaneous metastases without visceral metastases from an adenocarcinoma of the rectum

Skin metastasis from colorectal carcinoma without evidence of visceral metastases is exceedingly rare. However, it must be considered whenever a new skin growth appears in a patient with a history of carcinoma. A diagnostic biopsy is mandatory as the appearance of these metastases is not distinctive.     

Active specific chemoimmunotherapy of lymph-node metastasis from a poorly immunogenic murine fibrosarcoma

The fibrosarcoma MCA-SP, which was recently induced with methylcholanthrene (MCA) in C3H/HeJ mice, displays poor immunogenicity in in vivo prophylaxis. A cell variant MCA-SPN1, which bears a tumor-specific transplantation antigen (TSTA) cross-reactive with the parental line MCA-SP, was selected because of its proclivity for axillary lymph-node metastases. Although these lymph-node metastases were resistant to sinecomitant (post-excisional) immunity, they were susceptible to combined active and passive specific chemoimmunotherapy, using tumor-specific, 1-butanol-extracted, preparative isoelectric focusing-purified, TSTA (1 microgram weekly sc injections), cyclophosphamide (CY, a single intraperitoneal 20 mg/kg dose), and adoptive transfer of immune splenic T lymphocytes, which had been re-stimulated in vitro with extracted TSTA and interleukin-2. This triple regimen both reduced the incidence of spontaneous lymph-node metastases, and prolonged the survival of tumor-bearing, as well as tumor-resected hosts. The results from local adoptive transfer assay using T-lymphocyte subpopulations of spleen and lymph nodes in these treated hosts suggested that Lyt 2+ cytotoxic T-lymphocytes (CTL) mediated in vivo tumor-neutralization. Thus TSTA/CY/CTL therapy activates tumoricidal host responses effective against the poorly immunogenic MCA-SP tumor and its lymph-node metastases.     

Phase I clinical trial of fludarabine phosphate (F-ara-AMP)

Summary F-Ara-AMP (fludarabine phosphate) is an adenosine analogue that is resistant to deamination; it is a more potent cytotoxic compound than ara-A in experimental tumor systems. F-Ara-AMP was given by continuous IV infusion over 5 days once every 4 weeks to 27 evaluable adult patients with advanced cancer. The median Karnofsky performance status was 70% (range 50%–90%), and the median age was 58 years (range 41–74). In addition to adequate blood counts, a creatinine clearance of at least 60 ml/min was required. The initial dose level was 35 mg/m²/day. Dose-limiting myelosuppression was seen in the first patient. Subsequent patients were treated at lower doses. Myelosuppression was the only major toxicity. Leukopenia was generally more prominent than thrombocytopenia, but 2 patients experienced prolonged thrombocytopenia which prevented further therapy. Nausea was minimal, and neither renal nor neurologic toxicity was encountered. In patients with good renal function a dose of 25 mg/m²/day can be safely administered. However, because of apparent cumulative myelosuppressive effects a lower dose is more appropriate for patients who have had extensive prior chemotherapy or radiotherapy.Supported by CCPP grant CA-05826 and Contract NO1-CM-27546 from the National Cancer Institute, National Institutes of Health, Bethesda, Md. The content of this paper was presented in part at the 76^th meeting of the American Association for Cancer Research, Toronto, 1984     

Human high molecular weight melanoma-associated antigen (HMW-MAA) mimicry by mouse anti-idiotypic monoclonal antibody MK2-23: induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma.

Twenty-five patients with stage IV melanoma were immunized with the mouse anti-idiotypic monoclonal antibody (mAb) MK2-23 (2 mg per injection), which bears the internal image of the determinant defined by anti-HMW-MAA mAb 763.74. Two patients were inevaluable, since they did not complete 4 weeks of therapy. Only 14 patients developed antibodies that were shown by serological and immunochemical assays to recognize the same or spatially close determinant as the anti-HMW-MAA mAb 763.74 and to express the idiotope defined by mAb MK2-23 in their antigen-combining sites. Side effects that are likely to be caused by bacillus Calmette-Guérin present in the immunogen consisted of erythema, induration, and ulceration at the sites of the injections. Occasionally, patients complained of flu-like symptoms, arthralgias, and myalgias. Three of the patients who developed anti-HMW-MAA antibodies achieved a partial response. It consisted of a decrease in the size of metastatic lesions and lasted 52 weeks in 1 patient and 93 weeks in the other 2 patients. Survival of the 14 patients who developed anti-HMW-MAA antibodies was significantly (P = 0.0003) longer than that of the 9 patients without detectable humoral anti-HMW-MAA immunity development. In the multivariate analysis, such an association between development of anti-HMW-MAA antibodies and survival prolongation was still significant (P = 0.001) after adjustment for difference in performance status, the only confounding factor found to be significantly related to survival. Lastly, a significant (P = 0.03 by likelihood ratio test) interaction between anti-HMW-MAA antibodies and patients' performance status was found, since the prolongation of survival associated with anti-HMW-MAA antibodies was more marked in patients with a performance status of less than or equal to 70% than in those with a higher one. These results suggest that anti-idiotypic mAb MK2-23 may represent a useful immunogen to implement active specific immunotherapy in patients with melanoma.     

Active Specific Chemoimmunotherapy of Lymph-node Metastasis from a Poorly Immunogenic Murine Fibrosarcoma

The fibrosarcoma MCA-SP, which was recently induced with methylcholanthrene (MCA) in C3H/ HeJ mice, displays poor immunogenicity in in vivo prophylaxis. A cell variant MCA-SPN1, which bears a tumor-specific transplantation antigen (TSTA) cross-reactive with the parental line MCA-SP, was selected because of its proclivity for axillary lymph-node metastases. Although these lymph-node metastases were resistant to sinecomitant (post-excisional) immunity, they were susceptible to combined active and passive specific Chemoimmunotherapy, using tumor-specific, 1-butanol-extracted, preparative isoelectric focusing-purified, TSTA (1 fig weekly sc injections), cyclophosphamide (CY, a single intraperitoneal 20 mg/kg dose), and adoptive transfer of immune splenic T lymphocytes, which had been re-stimulated in vitro with extracted TSTA and interleukin-2. This triple regimen both reduced the incidence of spontaneous lymph-node metastases, and prolonged the survival of tumor-bearing, as well as tumor-resected hosts. The results from local adoptive transfer assay using T-lymphocyte snbpopulations of spleen and lymph nodes in these treated hosts suggested that Lyt 2⁺ cytotoxic T-lymphocytes (CTL) mediated in vivo tumor-neutralization. Thus TSTA/CY/CTL therapy activates tumoricidal host responses effective against the poorly immunogenic MCA-SP tumor and its lymph-node metastases.