Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes.

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.

Chronic oral etoposide and tamoxifen in the treatment of far-advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a chemoresistant tumor that frequently expresses a high level of p 170 glycoprotein of the multidrug-resistance (MDR) gene. Preliminary data suggested that VP-16 showed modest activity in HCC. Recently, schedule-dependent cytotoxicity of VP-16 has been demonstrated. In this study, we tested the therapeutic efficacy of chronic oral VP-16 plus tamoxifen, a potential MDR-reversing agent, in patients with far-advanced HCC. METHODS: A prospective single-arm study was conducted in the National Taiwan University Hospital. To be eligible, patients must have had unresectable and non-embolizable HCC, objectively measurable tumors, adequate hemogram with absolute granulocyte count greater than or equal to 2,000/mm3, and platelet count greater than or equal to 1x10 (5)/mm3, total serum bilirubin less than or equal to 3.0 mg/dl, age less than or equal to 75 years, and a Karnofsky performance status of greater then or equal to 50%. The treatment included VP-16 (Bristol-Myers-Squibb, Princeton, NJ), 50 mg/m2/day, orally, Days 1 to 21, and tamoxifen (Pharmachemie B.V. Haarlem, Netherlands), 40 mg/day, orally, Days 1 to 21; repeated every 5 weeks. RESULTS: Between December 1990 and December 1993, a total of 33 patients were enrolled in the study. There were 28 men and 5 women, with a median age of 51 years. They received an average of 3.2 (range: 1-10) courses of chemotherapy. ECOG (Eastern Cooperative Oncology Group) Grade 3 and Grade 4 leucopenia developed in 6 patients (18.2%) and 4 (12.1%) patients, respectively. Grade 3 and 4 thrombocytopenia developed in 2 patients (6.1%). Treatment-related death occurred in one patient due to sepsis. Mild gastrointestinal toxicities were common with Grade 1 and 2 nausea. Grade 1 and 2 vomiting, Grade 1 and 2 diarrhea, and Grade 1 and 2 stomatitis, developed in 13 (39.4%), 7 (21.2%), 12 (36.4%), and 16 (48.5%) patients, respectively. Grade 3 and 4 gastrointestinal toxicities were rare. Deep vein thrombosis occurred in one patient (3.0%). Eight patients (24.2%, 95% confidence interval 11%-42%) had achieved a partial remission, with a median time-to-progression of 6 months (2-11). Median survivals of the responders and non-responders were 8.0 and 3.0 months, respectively (P < 0.05). The median Karnofsky performance status of the responders improved from 70% to 80%. CONCLUSIONS: Chronic oral VP-16 and tamoxifen has modest activity and acceptable toxicity in far-advanced HCC, and is a useful palliative treatment in about a quarter of such patients.

[Testis yolk sec tumor--a case report].

A 16-months old normal boy, a right testicular mass was discovered incidentally by his grandmother. Right inguinal orchiectomy was performed. Histological examination showed yolk sac tumor of testis. A preoperative alpha-fetoprotein level was markedly elevated at 13568.9 ng/ml, by the end of the twelve postoperative months, the serum alpha-fetoprotein levels was 118 ng/ml. The patient is doing well one-year postoperatively.

Use of retinoic acids in the treatment of peripheral T-cell lymphoma: a pilot study.

PURPOSE: We have systemically analyzed, both in vitro and in vivo, the effect of 13-cis-retinoic acids (RA) on non-Hodgkin's lymphoma (NHL). METHODS: The in vitro growth-inhibitory effect of 13-cis-RA was examined in 11 (T cell, five; B cell, six) lymphoma cell lines by a tetrazolium colorimetric assay. A pilot clinical trial with oral 13-cis-RA 1 mg/kg/d was conducted in a selected group of 18 lymphoma patients, of whom 16 had failed to respond to at least one regimen of intensive chemotherapy. The in vitro and in vivo effects of 13-cis-RA were correlated with immunophenotypes, RA-induced changes of morphology, and patterns of DNA fragmentation of the lymphoma cells. RESULTS: Four of five T-lymphoma cell lines and none of six B-lymphoma cell lines were sensitive (concentration of 50% growth inhibition [IC50] < 1.5 microns) to 13-cis-RA (P = .015). In the clinical trial, five (two Ki-1, one angioinvasive type, one diffuse mixed cell, and one diffuse large cell) complete remissions and one (Ki1) partial remission were observed in 12 patients with peripheral T-cell lymphoma (PTCL), while none of six patients with B-cell lymphoma responded to 13-cis-RA. 13-cis-RA-induced cellular differentiation and apoptosis, as evidenced by the more mature morphology, characteristic nuclear condensation, and DNA ladder pattern signifying internucleosomal fragmentation, were demonstrated in the sensitive cell lines, as well as in the remitting lymphoma tissues. CONCLUSION: The 13-cis-RA appears to be active on lymphomas of T-lineage and their therapeutic indication may be extended to include some subtypes of PTCL. The mechanisms of action are related to differentiation and apoptosis of lymphoma cells. There appears to be no cross-resistance between 13-cis-RA and conventional chemotherapy.

Five-drug combination chemotherapy (FAPEL) for advanced gastric cancer: a pilot study.

To test if the incorporation of 5-fluorouracil (5-FU) and leucovorin in a modified etoposide, doxorubicin, cisplatin (EAP) regimen could diminish its toxicity and improve its efficacy, 18 patients with far-advanced, unresectable gastric cancer, diagnosed at National Taiwan University Hospital between January 1991 and December 1992, were treated with a FAPEL combination chemotherapy. The regimen consisted of doxorubicin 25 mg/m2 i.v. on day 1, cisplatin 60 mg/m2 i.v. infusion on day 1, etoposide 60 mg/m2/day i.v. infusion on days 1-3, 5-fluorouracil 500 mg/m2/day i.v. on days 1-3, and leucovorin 50 mg/day i.v. on days 1-3; repeated every three to four weeks. The patients included nine metastatic, six locally advanced and inoperable, and three post-gastrectomy recurrent cancer patients with median Karnofsky performance status of 60%. There were 11 men and seven women with a median age of 52.5 years. The patients tolerated the treatment toxicity relatively well and received an average of 4.3 courses of chemotherapy. Most patients completed the protocol therapy except one who refused and another who died of leucopenic sepsis. Myelosuppression was the limiting toxicity, with Eastern Cooperative Oncology Group (ECOG) grade 3-4 leucopenia developing in 35.9% and grade 3-4 thrombocytopenia developing in 11.5% of a total of 78 courses given. The overall objective response rate was 44.4% with 5.5% complete responses and 38.9% partial responses. The overall median survival was seven months (0.5-21 months). The median survival of responders and non-responders was 13 months (5-21 months) and three months (0.5-7 months), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Teratoma of testis--a case report].

A case of mature testicular teratoma in a 5-year-old child is presented. The level of serum beta-human chorionic gonadotropin (beta-HCG), alpha-fetoprotein (alpha-AFP), and carcinoembryonic antigen (CEA) were all within normal limit one year post-operatively. We discussed the clinical features, treatment and the result of this patient and reviewed the literature.