Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma.

PURPOSE: The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. PATIENTS AND METHODS: Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses. RESULTS: Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks. CONCLUSION: At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease.

Cardiac angiosarcoma: a case report.

Primary neoplasms of the heart are rare and difficult to diagnose prior to surgery, even with modern imaging techniques. Often, the tumors are diagnosed only at autopsy. Angiosarcoma is the most common malignant neoplasm. This disease is most commonly found in middle-aged men, and the tumor is most often located in the right atrium. It commonly causes blood flow abnormalities, extensively infiltrates cardiac structures, and may extend through the heart wall to involve adjacent structures. Metastatic spread at the time of diagnosis is common, and surgical mortality is high. We present a case of primary angiosarcoma involving the right ventricle of the heart. This tumor developed 6 months after the patient had undergone coronary artery bypass surgery. The patient was initially thought to have a massive thrombus within the right ventricle but at surgery was found to have a malignant neoplasm invading the myocardium. Subsequently, he was found to have pulmonary metastases. A debulking procedure was performed, and the patient was started on chemotherapy. Rather prompt improvement occurred after the debulking procedure, but subsequent studies have indicated progression of the pulmonary metastases despite ongoing chemotherapy.

Compliance with the recommendations of medical consultants.

Compliance with the consultant's recommendations is one measure of the effectiveness of a consultation. A previous study showed that compliance was better when fewer recommendations were made. In the subsequent year, consultants were encouraged to limit their recommendations to five or fewer. Despite a significant decrease in the number of recommendations, compliance rates remained essentially unchanged (72%). Multivariate analysis demonstrated that the clinical severity of the patient's disease and the number of associated problems, as well as the types of recommendations, were significant predictors of compliance. Compliance was best for recommendations involving medications (84%) and worst for recommendations involving diagnostic tests (62%). Compliance was also evaluated in the context of a surgeon's view of the appropriateness of the recommendations. For recommendations felt to be essential to patient care the compliance rate was 75%, but it was only 44% for recommendations judged nonessential (p less than 0.001). The consulting internist should be aware that the surgeon's view of the relevance of the recommendations to patient care needs may have an important effect on compliance.

Six-drug chemotherapy (hexamethylmelamine, doxorubicin, cisplatin, cyclophosphamide, methotrexate, and 5-FU; CHAMP-5) for ovarian carcinoma: alternating sequences of combination regimens.

Twenty-five patients with previously untreated adenocarcinoma of the ovary (International Federation of Gynecology and Obstetrics, stages II, III, and IV) were placed on a six-drug trial (CHAMP-5) for 18 months. This trial consisted of 28-day cycles of hexamethylmelamine, doxorubicin, and cisplatin alternating with hexamethylmelamine, cyclophosphamide, methotrexate, and 5-FU. After a minimum follow-up of 31 months, 14 (56%) of the 25 evaluable patients achieved complete or partial response and nine (36%) achieved complete pathologic response. Although CHAMP-5 is effective in the treatment of ovarian cancer, the results in these patients are not substantially different from those achieved with hexamethylmelamine, doxorubicin, and cisplatin alone.

Multiple myeloma--complete remission with high dose melphalan chemotherapy.

A patient with IgG3 lambda plasma cell myeloma characterized by anemia, hypercalcemia, hypoalbuminemia, renal insufficiency, osteolytic bone lesions, and serum and urinary light chains inadvertently received a dose of intravenous melphalan considerably greater than standard. A complete remission ensued characterized by normal protein and bone marrow studies. Healing of bone lesions occurred. This and two somewhat similar happenstances producing rare complete remissions in myeloma may have significant chemotherapeutic ramifications.