Camptothecin and podophyllotoxin derivatives: inhibitors of topoisomerase I and II - mechanisms of action, pharmacokinetics and toxicity profile.

Camptothecins represent an established class of effective agents that selectively target topoisomerase I by trapping the catalytic intermediate of the topoisomerase I-DNA reaction, the cleavage complex. The water-soluble salt camptothecin-sodium - introduced in early trials in the 1960s - was highly toxic in animals, whereas the semisynthetic derivatives irinotecan and topotecan did not cause haemorrhagic cystitis because of their higher physicochemical stability and solubility at lower pH values. Myelosuppression, neutropenia and, to a lesser extent, thrombocytopenia are dose-limiting toxic effects of topotecan.

Role of postchemotherapy surgery in the management of patients with liver metastases from germ cell tumors.

Objective: To evaluate the role of postchemotherapy adjunctive surgery in patients with liver metastases from germ cell cancer (GCT).

Patients And Methods: Forty-three male patients with nonseminoma were treated in different multicenter treatment protocols between 1990 and 1999, and they underwent hepatic surgery. The results of postchemotherapy surgical resection, histologic findings found during postchemotherapy surgery, and prognostic factors for survival were assessed.

New drug developments for patients with metastatic soft tissue sarcoma.

For the subgroup of patients with inoperable gastrointestinal stromal tumors, progress has been made by the rapid development and approval of the targeted therapy imatinib mesylate. Small round cell sarcomas (SRCT), such as Ewing/primitive neuroectodermal tumor, desmoplastic SRCT, and rhabdomyosarcoma, are chemotherapy-sensitive and potentially curable malignancies that are treated with multimodality dose-intensive neoadjuvant protocols regardless of size or overt metastatic disease. However, the number of effective cytotoxic agents for the treatment of patients with metastatic so-called adult soft tissue sarcoma is limited, especially when patients have failed anthracycline- and ifosfamide-based chemotherapy.

Comparative study of the acute nephrotoxicity from standard dose cisplatin +/- ifosfamide and high-dose chemotherapy with carboplatin and ifosfamide.

The nephrotoxic effects of different platinum compounds based combination chemotherapies were compared. Chemotherapy consisted of either cisplatin fractionated over 5 days (5 x 20 mg/m2) or given as a single-day infusion (1 x 50 mg/m2) plus ifosfamide (4 g/m2) or high-dose chemotherapy was applied including carboplatin (3 x 500 mg/m2) and ifosfamide (3 x 4 g/m2) fractionated over three consecutive days. Conventional parameters such as serum creatinine and glomerular filtration rate (GFR), as well as urinary protein excretion of N-acetyl-beta-D-glucosaminidase (NAG)) and alpha 1-micro-globulin were assessed in 52 patients.

A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation.

This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m(2)at day 1-3) given as a short infusion prior to carboplatin and ifosfamide.

A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based combination chemotherapy with or without amifostine in patients with solid tumors.

This study evaluates the degree of kidney damage during cisplatin/ifosfamide-based combination chemotherapy and its possible prevention by amifostine. Thirty-one patients with solid tumors stratified according to pretreatment were randomized to receive VIP- or TIP-chemotherapy with or without amifostine (910 mg/m2) given as a short infusion prior to cisplatin. Chemotherapy consisted of cisplatin (50 mg/m2), ifosfamide (4 g/m2) and either etoposide (500 mg/m2) (= VIP) or paclitaxel (175 mg/m2) (= TIP) repeated at 3 weekly intervals.

Phase II study of continuous 120-hour-infusion of mitomycin C as salvage chemotherapy in patients with progressive or rapidly recurrent gastrointestinal adenocarcinoma.

The aim of the study was to evaluate the therapeutic activity and safety of continuously infused (c.i.) mitomycin C in patients with metastatic gastrointestinal adenocarcinomas recurring after or progressing during chemotherapy.

The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors.

This study evaluates the degree of kidney damage during cisplatin/ifosfamide-based combination chemotherapy and its possible prevention by amifostine. Thirty-one patients with solid tumors stratified according to pretreatment were randomized to receive cisplatin/ifosfamide-based chemotherapy with or without amifostine (1000 mg absolute) given as a short infusion prior to cisplatin. Chemotherapy consisted of cisplatin (50 mg/m2), ifosfamide (4 g/m2) and either etoposide (500 mg/m2) (VIP regimen) or paclitaxel (175 mg/m2) (TIP regimen) repeated at 3 weekly intervals.

Platinum organ toxicity and possible prevention in patients with testicular cancer.

Advances in the management of metastatic testicular cancer are attributed mainly to the introduction of cisplatin into combination chemotherapy. In parallel with the development of effective chemotherapy resulting in long-term survival for the majority of patients, possible adverse effects of treatment have been systematically investigated. Besides acute side effects of cisplatin, such as gastro-intestinal toxic effects and moderate myelosuppression, reduction in glomerular filtration rate occurs in 20% to 30% of patients despite prophylactic intensive hydration and forced diuresis.