Phase II studies of Elsamitrucin in breast cancer, colorectal cancer, non-small cell lung cancer and ovarian cancer

PURPOSE:: To test the antitumor activity of Elsamitrucin in metastaticcancer of the breast, colon and rectum, non-small cell lungand ovary. PATIENTS AND METHODS:: Eligibility required histologically proven cancer. Patientswith colorectal or non-small cell lung cancer could not havereceived prior chemotherapy. Patients were entered if WHO PSwas 2 and organ functions were normal. Treatment consisted ofElsamitrucin 25 mg/m²/week given as a 5–10 min infusionfor at least 3–6 weekly doses. RESULTS:: One hundred and five patients entered the studies, 97 were eligible,94 are evaluable for toxicity and 75 for response. Toxicitymainly consisted of mild nausea/vomiting, and less frequentlyreversible hepatotoxicity and malaise. No objective responseswere seen. CONCLUSION:: Elsamitrucin at this dose and schedule is not an active drugin metastatic breast cancer, colorectal cancer, non-small celllung cancer or ovarian cancer. Elsamitrucin, phase II, breast, colorectum, nonsmall cell lung, ovary     

Zeniplatin in advanced malignant melanoma and renal cancer: phase II studies with unexpected nephrotoxicity

The antitumor activity of zeniplatin, a third-generation, water-soluble platinum compound that has shown broad preclinical antitumor activity and no significant nephrotoxicity in phase I trials, was tested in patients with advanced malignant melanoma and advanced renal cancer. Patients who had not previously been treated, except with local limb perfusion and immunotherapy, were given zeniplatin as bolus injections at 125 mg/m² every 3 weeks. The main hematological toxicity was leukopenia (7/30 patients, WHO grade ≥ 3) and the main nonhematological toxicity was nausea and vomiting (21/30 patients, WHO grade ≥ 2). Serious nephrotoxicity was observed early in the renal cancer study and, later, also in the melanoma study. Hyperhydration did not prevent the nephrotoxicity, and the studies were stopped after 6 renal cancer patients and 24 malignant melanoma patients had been included. Zeniplatin gave objective responses in 3 of the 21 evaluable malignant melanoma patients [2 complete responses (CRs) in patients with lymph-node metastases lasted 5 and 14 months, respectively; 1 partial response (PR) in a patient with lymph-node and liver metastases lasted 6 months]. In the renal cancer study, only four patients were evaluable for response and none responded. The results show that zeniplatin has some activity (14%) in patients with advanced malignant melanoma, but no conclusion can be drawn regarding the activity of zeniplatin in renal cancer as the number of patients was too low. The main toxicities were leukopenia and nausea and vomiting. Unexpected and serious nephrotoxicity was observed, and for this reason the studies were terminated before the planned number of patients had been included. A possible explanation for the nephrotoxicity may be drug interactions, but no firm conclusion can yet be drawn. Received: 16 March 1996 / Accepted: 25 March 1997     

Phase II study of 5′-deoxy-5-fluorouridine (doxifluridine) in advanced malignant melanoma

Summary Forty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m² daily ×5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m² in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts <1.5×10⁹/l leukocytes or 50×10⁹/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma.     

Use of and attitudes held towards unconventional medicine by patients in a department of internal medicine / oncology and haematology

A sizeable percentage of patients receiving conventional medical treatment also use unconventional medicine (UM). Surveys indicate that the prevalence of and motivation for the pursuit of the different approaches of UM is subject to individual, geographical, cultural and disease-related factors. We were interested in the concurrent use of and attitudes towards UM in patients who underwent conventional medical treatment in our oncologically orientated department of internal medicine in a regionally dominant teaching hospital. A representative sample (n = 131) of all inpatients and outpatients receiving treatment in the department or in its oncological/haematological outpatient clinic were asked to participate in a cross-sectional interview study on the use of unconventional therapies. In all, 128 patients (97.7%) agreed to participate in the study, and 65% of these patients were suffering from malignancies. Use of unconventional treatment was reported by 24% of all patients for their current medical problem, and 16% of the remaining patients had been thinking of adjunctive use. The use of UM was significantly higher among oncological patients (32%), and among oncological outpatients in particular (50%), than among patients with acute or chronic non-malignant diseases. Female patients predominated among the users of UM (71%). UM mainly took the form of various pharmacological and dietary approaches. Patients availing themselves of UM most frequently identified physicians (41%) as the source of treatment recommendation. Only 18% of the users of UM relied on these methods as a chance of cure. Use of UM was not generally motivated by dissatisfaction with conventional medical care. Only half the users informed their hospital physician of their adjunctive use of UM. Nearly 2 out of 3 of the users contended that UM had contributed to a mild or distinct improvement in their physical or psychological wellbeing. The use of UM in modern health care systems represents a widespread and intricate phenomenon, which cannot be understood by focusing exclusively on the objective assessment of clinical efficacy. Use of UM may be related more to a disease's unfavourable attribution than to its medically expected outcome. Coherence with individual illness paradigms and perceived efficacy are apparently important factors in patients' use of UM. These subjective aspects need to be recognised in caring patient-doctor communication.     

Docetaxel (Taxotere), a novel taxoid, in the treatment of advanced colorectal carcinoma: an EORTC Early Clinical Trials Group Study.

Docetaxel (Taxotere), a new semisynthetic taxoid, is a potentially important chemotherapeutic agent for the treatment of cancer. Forty patients with bidimensionally measurable advanced adenocarcinoma of the colon were treated with docetaxel 100 mg m-2 every 3 weeks as a 1 h infusion without routine premedication. Thirty-nine patients were eligible: 23 males and 16 females. Median age was 60 years (range 41-75) and WHO performance status 1 (0-2). Prior adjuvant chemotherapy was performed in four patients and prior radiotherapy in nine patients. Bidimensionally measurable disease sites included: liver in 26 patients, lymph nodes and abdominal/peritoneal masses in 13, lung/mediastinal masses in ten and subcutaneous nodes in four. The median number of cycles given was 2 (range 1-15). Thirty-three patients were evaluable for response. One patient (3%) achieved a complete response and two (6%) (95% confidence limits 0-14%) a partial response. Side-effects were similar to those observed in other studies. Docetaxel, given at this dosage and schedule, has minimal activity in the treatment of colorectal carcinoma.     

Chemotherapy of malignant bone tumors]

In several primary malignant tumors significant improvement of formely bad prognosis has been achieved by the introduction of new cytostatic compounds and the study of new cytostatic combination regimens. Adjuvant chemotherapy in osteosarcoma and Ewing's sarcoma led to remarkable increase in survival rates. Leaning on natural history and on remission rates reached by cytostatic treatment in metastasizing stages of disease, proposals for adjuvant chemotherapy are made and chemotherapy regimen appliable on out-patient basis is described.     

Randomized phase II trial of carminomycin versus 4'-epidoxorubicin in advanced breast cancer

Sixty-three evaluable patients with advanced breast cancer were randomly allocated to receive three-week intravenous courses of carminomycin (18 mg/m2) or 4'-epidoxorubicin (90 mg/m2). The former yielded one (3%) partial response for nine weeks among 29 patients whereas, in the other arm, nine (27%) of 34 patients achieved partial response for a median of 28 weeks (range, nine to 36 weeks; p less than 0.02). The major toxic effect of these anthracyclines was leukopenia with median white blood cell nadirs of 1,600/microL (range, 300-4,000/microL) versus 1,800/microL (range, 500-4,300/microL), respectively. Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia. Patients whose disease failed to respond to first-line anthracycline received doxorubicin (60 mg/m2) every three weeks. Four partial responses were obtained among 19 patients previously treated with carminomycin. Following 4'-epidoxorubicin therapy, one of 12 evaluable patients also attained partial response. Survival curves were not affected by the initial treatment option. Carminomycin has marginal activity against breast cancer whereas 4'-epidoxorubicin deserves further evaluation of its therapeutic index relative to doxorubicin. The design used in this trial appears attractive for prompt phase II evaluation of anthracycline analogs.     

A phase II study of Gemcitabine (LY 188011) in patients with advanced squamous cell carcinoma of the head and neck

BACKGROUND: Gemcitabine is a new pyrimidine antimetabolite with novel metabolicproperties and mechanism of action. Phase I clinical trialshave demonstrated acceptable toxicity and promising antitumoractivity. The objectives of this open multicenter phase II trialwere to determine the efficacy and toxicity of this agent inpatients with advanced head and neck cancer. PATIENTS AND METHODS: Sixty-one patients with advanced and/or recurrent squamous cellcarcinoma of the head and neck were treated with Gemcitabineas a weekly 30 minutes i.v. administration for 3 consecutiveweeks followed by one week rest. The Gemcitabine starting dosewas 800 mg/m²/week in 47 patients (a majority being pre-treatedwith chemotherapy) and was later increased to 1250 mg/m² in14 chemotherapy-naive patients. Dose adjustements were basedon hematologic and non-hematologic toxicities. RESULTS: Seven partial responses were observed among 54 evaluable patients,yielding a response rate of 13% (95% confidence interval: 4%–22%).The incidence of hematologic toxicity was low, with grade 3–4neutropenia in less than 10% of the courses. Fifty-three percentof the patients experienced an increase in liver enzymes, mainlygrade 1 or 2. Fatigue was reported by 39% of the patients, frequentlyassociated with flu-like symptoms. CONCLUSION: Gemcitabine is a drug with documented antitumor activity inpatients with advanced squamous cell carcinoma of the head andneck. head and neck cancer, gemcitabine, phase II study