Schedule- and dose-intensified paclitaxel as weekly 1-hour infusion in pretreated solid tumors: results of a phase I/II trial.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been studied primarily on a 3-week schedule as a 3-, 24-, or 96-hour infusion at doses ranging from 135 to 250 mg/m2. The observed toxicity profile seems to be both dose and schedule dependent. Dose densification of paclitaxel given weekly over 6 weeks on a split-dose schedule for an overall increase in dose intensity was thought to improve the therapeutic index of paclitaxel in a variety of advanced malignancies and to be suitable for outpatient administration. For this study, chemotherapy consisted of a weekly 1-hour infusion of paclitaxel at a starting dose of 40 mg/m2/wk for 6 weeks, followed by a 2- to 3-week interval. Paclitaxel dosage was escalated in 10 mg/m2/wk increments in subsequent patients, to a maximum dosage of 90 mg/m2/wk. Intravenous dexamethasone, cimetidine, clemastine, and ondansetron were administered immediately before the paclitaxel infusion. Fifty patients participated in the study. The male to female ratio was 21 to 29, the median age was 53.2 years (age range, 33 to 74), and the median performance status was 1. All patients were chemotherapeutically pretreated. Overall response included five complete responses (10%), 15 partial responses (30%), 19 no change (38%), and 11 disease progressions (22%). Median dose intensity was 410 mg/m2/6 wk (range, 200 to 540 mg/m2/6 wk). Hematologic toxicity was mild, with no grade 3 or 4 toxicity up to 90 mg/m2/wk. No hypersensitivity reactions or neurologic or cardiac toxicities were documented. Dose-densified, weekly paclitaxel is concluded to be active in a variety of pretreated tumor entities. The overall low hematologic and peripheral toxicity profile suggests that further dose intensification of weekly paclitaxel and/or combination with other cytotoxic agents (eg, cisplatin/carboplatin, ifosfamide, etoposide) may be warranted. Paclitaxel can be given safely in the outpatient setting. Paclitaxel 90 mg/m2/wk is recommended for single-agent treatment. Dose-densified paclitaxel may be considered a valuable and promising alternative to standard 3-week treatment, with further options possible in combination chemotherapy.

Ambulatory high-dose 5-day continuous-infusion ifosfamide combination chemotherapy in advanced solid tumors: a feasibility study.

The oxazaphosphorine analog ifosfamide (IFO) has demonstrated an increased therapeutic index in a variety of solid tumors and hematologic malignancies compared with its parent compound cyclophosphamide. A fractionated dose schedule over 5 days as continuous infusion in combination with the uroprotective agent sodium-2-mercapto-ethane-sulfonate (mesna) is considered to provide an improved therapeutic/toxic ratio. Stability data of IFO demonstrate long-term stability for use in disposable infusion pumps as outpatient treatment. In all, 52 patients with various malignancies were entered in a feasibility study to receive outpatient continuous infusion of IFO. All patients were required to have a subcutaneous venous port system implanted. The following drug combinations were used: IFO as single agent, IFO/mitoxantrone, IFO/carboplatinum/etoposide, IFO/etoposide/MTX, IFO/epirubicin. Mitoxantrone and epirubicin were given as continuous infusion together with IFO. Starting dose of IFO was between 1.6-2.0 g/m2/day x 5 and was increased in absence of major hematologic or peripheral toxicity. Mesna was given in combination with IFO as continuous infusion at a dose of 50% of that calculated for IFO. No renal, bladder or central nervous system toxicity was observed. In 247 courses of outpatient continuous ifosfamide infusion only few technical complications due to improper handling were documented.

[A case each of complete duplication of the stomach and of the duodenum (author's transl)]. / Je ein Fall von vollständiger Duplikatur des Magens und des Duodenums.

Previous reports of the very rare observations concerning complete duplication of the stomach and of the duodenum are reviewed and such a case is described. Radiological examination and gastroscopy showed complete duplication of the stomach, the abnormal organ being situated dorsal to the normal stomach and communicating with it at three separate points--fornix, body and antrum, and also through a duodenal diverticulum. In addition the authors describe complete duplication of the bulb and descending part of the duodenum, connecting through a duodenal diverticulum. The pathogenesis of these duplications and their relationship to duodenal diverticula is discussed.

[Primary adenocarcinoma of the duodenum. Clinical picture and radiological findings]. / Primäres Adenokarzinom des Duodenums. Klinik und radiologische Befunde.

The clinical and radiological features of primary adenocarcinoma of the duodenum are demonstrated by seven histologically confirmed cases. Clinically, obstruction develops following a prolonged uncharacteristic prodromal stage. The radiological findings resemble those of a carcinoma in any other part of the gastro-intestinal tract: polypoid filling defects, ulcers, mural thickening and loss of elasticity. The radiological method of choice is hypotonic duodenography. Sonography and CT are complimentary methods and are of use in postoperative follow-up.

Chemotherapy of advanced and relapsed squamous cell cancer of the head and neck with split-dose cisplatinum (DDP), 5-fluorouracil (Fura) and leucovorin (CF).

58 patients with locally advanced or relapsed squamous cell head and neck cancer were treated on 5 consecutive days with DDP 20 mg/m2/d IV-push, followed by CF 100 mg/m2/d IV-bolus and Fura 400 mg/m2/d IV-push 60 minutes later. Treatment was recycled on day 22(-29), according to toxicity. CF was added to the widely used DDP/Fura combination, because recent studies showed enhancement of Fura-activity by CF. 45/58 patients had no prior therapy and 13/58 pts were relapsed after chemotherapy and/or radiation therapy. All patients were evaluable for toxicity and response. After 3 courses of induction chemotherapy 23/45 pts in the previously untreated group had a complete response (CR); 20/45 a partial response (PR), 2/45 were restaged as no change (CR + PR: 95%). Induction chemotherapy was followed by radical surgery and postoperative radiation therapy. In the pretreated group 4/13 pts had a complete response; 6/13 a partial response; no change in 3/13 pts. Median duration of remission (MDR) has not been reached in the primarily untreated group, whereas in pretreated patients the MDR was 3.8 months (range 2.3 - 11.7 months). Hematologic and gastrointestinal toxicity was substantial but manageable and therapy was performed on an outpatient basis. The combination of DDP, CF and Fura has high activity in untreated and pretreated head and neck cancer patients. The obtained results are comparable to the widely used DDP/Fura continuous infusion regimen.

[Results of preoperative radio-chemotherapy in locally advanced squamous epithelial cancer of the esophagus]. / Ergebnisse der präoperativen Radio-Chemotherapie beim lokal fortgeschrittenen Plattenepithelcarcinom des Oesophagus.

In a 4-year period (1988-1991) 122 patients with a squamous cell carcinoma of the esophagus were studied prospectively and analysed. 64 patients of them could be primary resected (primary resectability rate 52%), 36 patients were in general inoperable and 22 patients had an advanced stage of cancer with local inoperability. Due to a preoperative combined radiotherapy and chemotherapy 16 of the 22 patients with local inoperability had a clinical remission of the tumor (73%). 11 patients (50%) showed a histological verified down staging and 3 cases of them a complete remission (no primary tumor was found, no infiltration of the regional lymphnodes and no metastatic disease). Curative resection was possible in 14 of 16 patients with clinical remission (2 patients refused surgical treatment). So the resectability rate now increases from 52 to 63%. We conclude that there was no increased rate of postoperative complications or mortality in the combined radio-/chemotherapy group compared with the primary resected patients.