Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.      

Langerhans' cell histiocytosis with thyroid involvement masquerading as thyroid carcinoma

A 28-year-old woman was admitted to our Hospital with a chief complaint of progressive gingival swelling and loosening of teeth over about a year. According to past history, she had received total thyroidectomy 2 years previously due to thyromegaly. The thyroidectomy specimen was at first interpreted as 'poorly differentiated carcinoma of the thyroid'. One year ago, she began to be aware of gingival swelling and loosening of teeth. A gum biopsy was taken and the pathologic features were similar to her 'thyroid carcinoma'. Subsequent investigations, including immunohistochemical stain, showed the gum was heavily infiltrated with histiocyte-like Langerhans' cells which were positive for S-100 protein. Ultrastructural examination of the cells under electron microscope revealed many typical intra-cytoplasmic Birbeck granules. Langerhans' cell histiocytosis was diagnosed. Langerhans' cell histiocytosis with thyroid involvement is extremely rare and may run a relatively indolent course. Even on a retrospective examination, it may easily be confused with poorly differentiated carcinoma of the thyroid. We suspect that this error may have been made on other occasions and that the occurrence of this condition may be underreported.      

Treatment related deaths during induction and in first remission in acute lymphoblastic leukaemia: MRC UKALL X

The benefits of achieving a long term event free survival of 60-70% by using increasingly intense treatment regimens must be weighed against the increased risk of treatment toxicity. From 1985 to 1990, 1612 children with childhood acute lymphoblastic leukaemia (ALL) in the UK were treated on MRC UKALL X with intensive induction therapy, central nervous system directed therapy (cranial irradiation and intrathecal methotrexate), and continuing treatment for two years. There was a randomisation to receive blocks of additional intensification treatment at five weeks, 20 weeks, not at all, or both. The five year disease free survival was 71% for children randomised to two blocks of intensification, a 14% improvement on children randomised to no intensification treatment. Treatment related mortality in this national multicentre study has been analysed for induction and first remission (including those after intensification treatment). There were 38 induction deaths, 2.3% and 53 deaths in first remission, 3.3% (including those from a second malignancy). Thirty one (84%) of the induction deaths followed an infection: bacterial in 22 and fungal in nine. Thirty seven infective remission deaths occurred: bacterial in 11, viral in 16, fungal in seven, and three caused by Pneumocystis carinii pneumonia. Ten of these deaths followed a block of intensification treatment. The majority of noninfective remission deaths followed the development of a second tumour. Risk analysis for an induction death showed girls and children with Down's syndrome to be at greater risk. For deaths in first remission analysis showed an increased risk for bone marrow transplant (BMT) patients and children with Down's syndrome. There was no effect of age and leucocyte count for either group. Most significantly when BMT patients were excluded from the analysis, intensification treatment did not increase the risk of remission death.     

Paclitaxel-containing high-dose chemotherapy in high-risk breast cancer patients

Despite standard-dose adjuvant chemotherapy, the prognosis for patients with breast cancer and extensive axillary lymph node involvement at diagnosis is poor. The efficacy of a paclitaxel-containing, high-dose chemotherapy protocol in 21 high-risk breast cancer patients is assessed. After standard-dose chemotherapy followed by peripheral blood stem cell (PBSC) mobilization, high-dose therapy with paclitaxel, carboplatin, and cyclophosphamide and CD34-selected PBSC rescue was given. Hematologic reconstitution after high-dose therapy was rapid. Main toxicity included diarrhea grade I or II in about half of the patients and infections were observed in 19%. Five-year probabilities for relapse and failure-free survival were 32% and 62%, respectively. High-dose consolidation with paclitaxel, carboplatin, and cyclophosphamide achieves a high failure-free survival in patients with high-risk breast cancer with acceptable toxicities and stable, long-term hematopoietic reconstitution. Evaluation of the benefit of high-dose therapy in these patients in larger prospective, randomized trials is warranted and currently under way.     

Detection of minimal residual disease in patients with cancer: a review of techniques, clinical implications, and emerging therapeutic consequences

The issue of minimal residual disease (MRD) manifesting itself by the presence of undetected disseminated isolated tumor cells in both tissues and hematopoietic autografts from patients with early-stage malignancies or from patients in clinical complete remission has been discussed widely during the last decade. Based on the current understanding of the pathogenesis of malignancy, disseminated tumor cells persisting after conventional oncologic treatment modalities or after reinfusion of contaminated autologous hematopoietic cells constitute the source of subsequent recurrence of disease. Accordingly, much emphasis is placed on the detection and characterization of disseminated isolated tumor cells in both basic and clinical research. This effort is aimed at a better understanding of the processes of metastasis and tumor dormancy and, ultimately, the estimation of prognosis, molecular monitoring, and the design of new therapeutic agents in oncology. In our review, we used computerized (MEDLINE, Embase) and manual searches to summarize laboratory and clinical data concerning MRD focusing on the issue of MRD in solid malignancies. We give a detailed overview of the methods used for the detection and molecular characterization of disseminated tumor cells and of the prevalence and prognostic significance of the detection of MRD in patients and hematopoietic autografts. Finally, we discuss the emerging therapeutic consequences of the detection of disseminated tumor cells, with special emphasis on the therapeutic potential of antibodies. We conclude that the detection of MRD represents a hallmark for the diagnosis, monitoring, and treatment of malignant conditions in future clinical trials.     

Intensified Adjuvant IFADIC Chemotherapy for Adult Soft Tissue Sarcoma: A Prospective Randomized Feasibility Trial

Purpose. The present prospective randomized adjuvant trial was carried out to compare the toxicity, feasibility and efficacy of augmented chemotherapy added to hyperfractionated accelerated radiotherapy after wide or marginal resection of grade 2 and grade 3 soft tissue sarcoma (STS).Patients and methods. Fifty-nine patients underwent primary surgery by wide or marginal excision and were subsequently randomized to receive radiotherapy alone or under the addition of six courses of ifosfamide (1500 mg/m(2) , days 1-4), dacarbazine (DTIC) (200 mg/m(2) , days 1-4) and doxorubicin (25 mg/m(2) , days 1-2) administered in 14-day-intervals supported by granulocyte-colony stimulating factor (30 x 10(6) IU/day, s.c.) on days 5-13. According to the randomization protocol, 28 patients received radiotherapy only, whereas 31 patients were treated with additional chemotherapy.Results. The relative ifosfamide-doxorubicin-DTIC (IFADIC) dose intensity achieved was 93%. After a mean observation period of 41+/-19.7 months (range, 8.1-84 months), 16 patients (57%) in the control group versus 24 patients (77%) in the chemotherapy group were free of disease (p>0.05).Within the control group, tumor relapses occurred in 12 patients (43%;six patients with distant metastases, two with local relapse, four with both) versus seven patients (23%; five patients with distant metastases, one with local recurrence, one with both) from the chemotherapy group. Relapse-free survival (RFS) (p=0.1), time to local failure (TLF) (p=0.09), time to distant failure (TDF) (p=0.17) as well as overall survival (OS) (p=0.4) did not differ significantly between the two treatment groups. Treatment-related toxicity was generally mild in both treatment arms.Conclusion. We conclude that the safety profile of intensified IFADIC added to radiotherapy was manageable and tolerable in the current setting. Inclusion of intensified IFADIC was not translated into a significant benefit concerning OS, RFS, TLF andTDF as compared with radiotherapy only, although a potential benefit of chemotherapy for grade 3 STS patients needs to be validated in prospective randomized trials including larger patient numbers.     

Roxatidine versus ranitidine in the treatment of duodenal ulcers: A randomized double-blind controlled multicentre study in Singapore

Roxatidine acetate, a new H₂ receptor antagonist, was compared with ranitidine in the treatment of duodenal ulcers in a double-blind multicentre study. Eighty-four patients with endoscopically proven duodenal ulcer were randomized to receive 150 mg roxatidine acetate or 300 mg ranitidine at bedtime. Repeat endoscopy was performed after 4 weeks (25–33 days) and if the ulcer had not healed, another endoscopy was performed after a further 4 weeks of treatment. Using per protocol analysis 73.6% of ulcers treated with roxatidine healed at 4 weeks compared to 72.2% of ulcers treated with ranitidine (P=NS). The healing rates at 8 weeks were 92% with roxatidine and 83.3% with ranitidine (P=NS). Using equivalence tests, the healing rate of roxatidine was found to be equivalent to that of ranitidine within a 20% region. Roxatidine users took significantly less antacids than ranitidine users (P < 0.05). There were no significant adverse effects due to roxatidine or ranitidine. Roxatidine is a safe effective drug in the treatment of duodenal ulcers with a healing rate comparable to that of ranitidine.