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Biomedical subjects

K Ramming

Publications and source records attributed to K Ramming.

11 recordsLinked to original sources

Effective chemotherapy for melanoma after treatment with interleukin-2.

Twenty patients with biopsy-proven metastatic malignant melanoma, previously treated with interleukin-2 (IL-2), received combination chemotherapy for progressive disease. Treatment included carmustine, cisplatin, dacarbazine, and tamoxifen (BCDT). Nausea was the most common toxicity (100%) and usually was mild. Persistent thrombocytopenia was the most frequent toxicity limiting further treatment. Eleven patients (55%) had an objective partial response, three patients (15%) had a minor response, and six patients (30%) had no change or progressive disease in response to this treatment. These results were comparable to the high response rates (21 of 40, 53%) achieved with BCDT in previously untreated patients with melanoma. It was concluded that prior therapy using IL-2 does not significantly alter the response rate of metastatic melanoma to BCDT, thus suggesting that immunomodulators (e.g., IL-2) and chemotherapeutic agents are not cross-resistant treatments.

Adult↗

Sequential chemoimmunotherapy in the treatment of metastatic melanoma.

PURPOSE: A phase II study that alternates the sequence of chemotherapy (carmustine [BCNU], cisplatin [CDDP], and dacarbazine [DTIC]) and biologic therapy (interleukin-2 [IL-2] and interferon alfa-2 alpha [alpha IFN]) was performed to establish a safe and efficacious way to sequence these forms of treatment for metastatic melanoma. PATIENTS AND METHODS: Patients who had measurable metastatic melanoma, a Karnofsky performance status of greater than or equal to 70, and no clinically significant cardiac or pulmonary dysfunction were eligible for entry onto this trial. Responses to treatment were assessed after a treatment cycle by two tumor evaluations at least 4 weeks apart. RESULTS: Forty-two consecutive patients with metastatic melanoma were treated with this sequential chemoimmunotherapy. Transient thrombocytopenia and neutropenia were observed frequently, but neither hemorrhage nor infection occurred in any of the patients. Of the 42 patients, 10 achieved a complete response (24%), 14 achieved a partial response (33%), two achieved a minor response (5%), eight had stable disease (19%), and eight (19%) had progressive disease. The median time to disease progression for all patients was 7 months. The median survival for all patients entered onto the trial was 11.5 months. A vitiligo-like depigmentation was induced in many patients by this treatment. CONCLUSIONS: Cytotoxic chemotherapy can be administered safely immediately before or immediately after IL-2 and alpha IFN. Sequential chemoimmunotherapy administered as previously described yields a response rate of more than 55%. The overall survival curve suggests that a proportion of patients may achieve a long-term benefit from this treatment. Also, cutaneous depigmentation induced by this treatment suggests that immune modulation may contribute to the antimelanoma effect of this treatment.

Adult↗

The elusive colonic malignancy. A need for definitive preoperative localization.

Colonoscopy with biopsy is the standard of practice for the diagnosis of colonic malignancies. Unfortunately, the inability of endoscopy to obtain precise distance measurements from the anal verge can make localization of lesions at operation difficult. For this reason, preoperative barium enema or intraoperative colonoscopy have been advocated to further pinpoint the sites of those lesions not thought to be easily located at operation. Five patients are presented in whom malignant lesions of the colon were diagnosed and verified histologically, but were later undetectable at operation or subsequent colonoscopic examinations. Four of these patients underwent laparotomy and three received colon resections. None of these patients' tumors were identified during intraoperative colonoscopy, in the resected bowel on pathologic examination, or on follow-up colonoscopy. A fifth patient is presented who spontaneously passed a polyp containing invasive adenocarcinoma, but multiple colonoscopic examinations have failed to identify the site of the lesion. To date, none of these tumors have recurred with periods of follow-up ranging from 6 months to 2 years. These patients demonstrate a poorly documented and little understood aspect of the behavior of colonic malignancies, i.e., the ability to spontaneously regress or slough from the bowel wall. Based on these instances, localization of potentially malignant colon lesions is recommended with submucosal dye injections at initial endoscopy or with colonoscopy in the operating room immediately prior to operation.

Aged↗

Phase I study of weekly 24-hour infusions of recombinant human interleukin-2.

Sixteen patients with metastatic melanoma or metastatic renal cell carcinoma were treated with six weekly 24-hour infusions of recombinant interleukin-2. At least three patients were treated at each dose, beginning at 3.0 mU/m2 for 24 hours each week for 6 weeks. Subsequent patients were treated at 4.5, 6.0, 8.0, and 10.0 mU/m2 for 24 hours. The incidence of diarrhea, rigors, rash, edema, and symptomatic hypotension was positively correlated with dose level. Symptomatic hypotension was dose limiting at the 10-mU/m2 level. Fever, nausea, and vomiting were seen at each dose level and could not be correlated with dose level. Lymphopenia and eosinophilia were observed at the completion of each 24-hour infusion, and an increase in peripheral blood absolute lymphocytes and eosinophils was observed over the 6-week treatment period. No thrombocytopenia was observed. No change in delayed-type hypersensitivity (type IV) as determined by skin testing could be demonstrated at any dose level. Natural killer cell cytotoxicity of peripheral blood lymphocytes increased over the treatment period, but the increase was unrelated to dose level in the range studied. One minor response was documented in a patient with renal cell carcinoma.

Adult↗

Branch patch for arterialization of hepatic grafts.

Arterial revascularization is essential for graft survival in transplantation of the liver. The "branch-patch" technique described herein simplifies this small anastomoses. Fifty-two pig and human transplants have been performed resulting in 100 per cent patency. This approach may also be suitable for other small arterial anastomoses.

Animals↗

Intranuclear branched cylindrical structures in human osteosarcoma cells.

A peculiar branched cylindrical structure within the nuclei of human osteosarcoma cells is reported. Although the described structures may be postulated to represent either "vermicellar bodies" or a response to cellular injury by chemotherapeutic agents, their origin and function are unknown to us.

Adult↗

CEA monitoring among patients in multi-institutional adjuvant G.I. therapy protocols.

The Gastrointestinal Tumor Study Group (GITSG) has since 1975 included protocols for monitoring carcinoembryonic antigen (CEA) levels in its colorectal cancer adjuvant trials. Among the 563 patients on the colon cancer study (GI 6175) and the 207 patients on the rectal cancer study (GI 7175), one third had preoperative CEA determinations and more than 90% had some postoperative CEA monitoring. Colon cancer patients whose preoperative CEA was greater than 5 ng/ml had a greater probability of recurring than those whose values were lower (33% versus 18% recurrence with 21 months minimum follow-up; p < 0.05). The prognostic value of preoperative CEA was apparent only in patients with Dukes' C1 colon tumors. Preoperative CEA values were not of prognostic significance among the rectal adenocarcinoma patients. Although elevated levels of CEA after resection of either colon or rectum cancers were strongly associated with subsequent tumor recurrence, no single CEA value, arbitrarily defined as "elevated", provided an adequate screening test with both high sensitivity and high specificity. Postoperative CEA elevations were more strongly predictive of recurrence when part of a steadily rising trend. In the colon cancer study, the median monthly increase in CEA for disease-free patients was estimated to be zero, and for the relapsed patients 5.8%. The corresponding estimates for patients on the rectal cancer protocol were zero and 7.8%. Only 36 of the 344 disease-free patients on the colon protocol and 14 of the 94 disease-free patients on the rectal protocol (15%) exhibited a rate of increase of CEA as high as 3% per month over the entire period of observation. Two thirds of the relapsed patients on both studies showed a rate of increase this high or higher. The patterns of CEA rise in individual patients were quite varied, however, and monthly rates of increase as established in our study are not to be used as guidelines in patient management.

Carcinoembryonic Antigen↗

Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group.

One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

Adenocarcinoma↗

Randomized phase II clinical trial of adriamycin, methotrexate, and actinomycin-D in advanced measurable pancreatic carcinoma: a Gastrointestinal Tumor Study Group Report.

Sixty-six patients with advanced pancreatic carcinoma were randomized to receive single agent chemotherapy with either adriamycin, methotrexate, or actinomycin-D using conventional dose, route and schedule of administration. All patients had measurable lesions which were used to objective assessment of response. For adriamycin, 2 of 25 patients (8%) evidenced a partial response (2 of 15 (13%) previously untreated patients). One of 25 patients treated with methotrexate and one of 28 received actinomycin-D responded. The duration of responses ranged from 43-64 days for those patients with no chemotherapy prior to study entry. The median survival of patients who received adriamycin as initial treatment was 12 weeks compared to 8 weeks for methotrexate and 6 weeks for actinomycin-D therapy.

Adult↗

BCG immunotherapy as a systemic adjunct to surgery in malignant melanoma.

Results of our study suggest that BCG systemic adjuvant immunotherapy may be effective for improving both the recurrence and survival rates in patients with regional metastases from malignant melanoma. BCG is more effective in patients with small amounts of subclinical disease. It is apparent from results of clinical trials that many of the principles derived from the study of animal tumor systems are applicable to human cancer in that immunotherapy is most effective for a small residual number of tumor cells. BCG treatment fulfills many of the ideal criteria for adjuvant treatment following surgery. It is relatively nontoxic; it is effective for disseminated melanoma; it has systemic activity in the adjuvant treatment of subclinical metastases. Hwever, until clinical trials are complete, this treatment as adjuvant therapy must be considered investigational.

Animals↗