Marine cyanobacteria—a prolific source of natural products

Systemic therapy for renal cell carcinoma

Disulfideand Multisulfide-Containing Metabolites from Marine Organisms Cheng-Shi Jiang, Werner E. G. M€uller, Heinz C. Schr€oder, and Yue-Wei Guo* State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang High-Tech Park, Shanghai 201203, People’s Republic of China Institute for Physiological Chemistry, Medical Center of the Johannes Gutenberg-University, Duesbergweg 6, D-55128 Mainz, Germany

Disulfide- and multisulfide-containing metabolites from marine organisms.

Cytotoxic chemotherapy for advanced renal cell carcinoma.

Recent advances in the discovery and development of topoisomerase inhibitors as antitumor agents

The combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) was reported to be effective in patients with metastatic transitional cell cancer of the urinary bladder. This study was designed to test the effectiveness of the phase II agent amsacrine (m-AMSA) versus CAP in patients previously untreated with systemic chemotherapy, with crossover if no response occurred or at the time of progression. In 23 patients who were randomized to receive CAP, three achieved complete response, seven achieved partial response, six had stable disease, and seven had disease progression. The responses in the 22 patients who received m-AMSA were: one with complete response, three with partial response, six with stable disease, and 12 with progressive disease. The overall response rate to initial CAP therapy was 43% compared to 19% for initial m-AMSA therapy. The median duration of response to CAP was 28 weeks and to m-AMSA was 21 weeks. There were no statistically significant differences in the durations of response or survival times between the groups. The main side effects of CAP were: nausea and/or vomiting, leukopenia, anemia, thrombocytopenia, and renal toxicity. Leukopenia and anemia were the major toxic effects of m-AMSA. Our study supports the justification for testing phase II agent(s) in previously untreated patients with bladder cancer with systemic chemotherapy, provided adequate crossover to a known active single or combination of agents is built into the design of such a trial.

Phase II trial of cyclophosphamide, doxorubicin, and cisplatin (CAP) versus amsacrine in patients with transitional cell carcinoma of the urinary bladder: a Southwest Oncology Group study.

The Southwest Oncology Group studied the response rate and toxicity of didemnin B (3.47 mg/m2 i.v. q 28 days) in patients with advanced renal cell carcinoma. There were no responses in 22 response evaluable patients. Toxicity was significant with 10 patients having grade 3 or 4 toxicity. Toxicity seen included nausea and vomiting, exacerbation of coronary artery disease, hyperglycemia, anorexia, diarrhea and hepatitis. Didemnin B was toxic but inactive in patients with renal cell treated at this dose.

Phase II evaluation of didemnin B in advanced adenocarcinoma of the kidney. A Southwest Oncology Group study.

Evaluation of fludarabine phosphate in renal cell carcinoma: a southwest oncology group study

Twenty four patients with advanced renal cell carcinoma were treated in a phase II trial with amonafide 300–450 mg/m2/day on days 1–5 every 21 days. There were no responders, 6 patients had stable disease, 14 experienced progressive disease and 4 were assumed to be non-responders as no evaluation was performed. There were no fatal toxicities although 8 patients had grade 3 or 4 granulocytopenia, 1 patient had grade 4 thrombocytopenia. Other toxicities included grade 3 diarrhea in 1 patient, grade 3 myopathy in 1 patient, severe nausea and vomiting in 1 patient and a facial rash, possibly a hypersensitivity reaction, in 1 patient. The median survival is 7.5 months. At this dosage and schedule, there is no evidence that amonafide has meaningful anti-tumor activity in patients with advanced renal cell carcinoma.

Phase II evaluation of amonafide in renal cell carcinoma. A Southwest Oncology Group study.

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of piroxantrone (150 mg/m2 q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 32 eligible patients, there were no partial nor complete responses. There were two mixed responses. Significant white cell toxicity, anemia, nausea, and vomiting were observed. Mild or moderate degrees of fever, malaise, and stomatitis occurred. No significant cardiac toxicity was noted. Piroxantrone does not have significant activity as a single agent in advanced renal cell carcinoma.

/pdf/phase-ii-evaluation-of-piroxantrone-in-renal-cell-carcinoma-2z0ngxwzao.pdf

Phase II evaluation of piroxantrone in renal cell carcinoma. A Southwest Oncology Group Study.

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