Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study.

BACKGROUND: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered. PATIENTS AND METHODS: Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level. RESULTS: Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118). CONCLUSIONS: The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status.

Quality of life of patients receiving platinum-based chemotherapy plus cetuximab first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: A phase III trial demonstrated that cetuximab is the first agent in 30 years to improve survival when added to platinum-based chemotherapy (platinum-fluorouracil) first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). This analysis of the trial assessed the impact of treatment on quality of life (QoL). PATIENTS AND METHODS: The European Organisation for Research and Treatment of Cancer QoL Questionnaire-Core 30 (QLQ-C30) and QLQ-Head and Neck 35 (QLQ-H&N35) module were used to assess QoL. RESULTS: Of 442 patients randomly assigned, 291 (QLQ-C30) and 289 (QLQ-H&N35) patients completed at least one evaluable questionnaire. For QLQ-C30, cycle 3 and month 6 mean scores for platinum-fluorouracil plus cetuximab were not significantly worse than those for platinum-fluorouracil. Pattern-mixture analysis demonstrated a significant improvement in the global health status/QoL score in the cetuximab arm (P = 0.0415) but no treatment differences in the social functioning scale. For QLQ-H&N35, the mean score for the cetuximab arm was not significantly worse than that for the chemotherapy arm for all symptom scales at all post-baseline visits. At cycle 3, some symptom scores significantly favored the cetuximab arm (pain, swallowing, speech problems, and social eating). CONCLUSION: Adding cetuximab to platinum-fluorouracil does not adversely affect the QoL of patients with recurrent and/or metastatic SCCHN.

Risk-adapted treatment choice in stage I nonseminomatous testicular germ cell cancer by regarding vascular invasion in the primary tumor: a prospective trial.

Based on the results of a retrospective study, which found blood vessel invasion to be the most important prognostic factor in clinical stage I nonseminomatous testicular germ cell cancer (NSTGCC I), a prospective study was started in 1985 which assigned NSTGCC I patients without evidence of vascular invasion to surveillance and patients with vascular invasion to two cycles of adjuvant chemotherapy with cisplatin, etoposide, and bleomycin. Twenty-two patients entered the surveillance group and 18 patients received adjuvant chemotherapy. Median follow-up is 30 months (3 to 50 months). Relapses occurred in three patients (7.5%), one in the surveillance group (4.5%), two in the chemotherapy group (11%). Thirty-eight patients (95%) are alive and without evidence of disease. Two patients of the adjuvant-treated group died, one of progressive germ cell cancer and one of lung cancer. We conclude that low- and high-risk NSTGCC I patients can be identified by considering blood vessel invasion. The presence of embryonal carcinoma and vascular invasion seem to be interrelated prognostic factors, because in 94% of vessel invasion the invading element was embryonal carcinoma. The exclusion of patients with vascular invasion from surveillance decreases relapse rates remarkably. Adjuvant chemotherapy diminishes relapse rates in high-risk patients but does not entirely prevent relapse.

Efficacy and toxicity of 2-Chlorodeoxyadenosine (Cladribine)--2 h infusion for 5 days--as first-line treatment for advanced low grade non-Hodgkin's lymphoma.

2-Chlorodeoxyadenosine (Cladribine) is a new purine analogue with high activity in pretreated low grade non-Hodgkin's lymphoma (NHL). To evaluate the efficacy of this drug in untreated patients with advanced NHL, we performed a prospective multicentre trial. Cladribine (0.12 mg/kg) was administered intravenously daily for 5 consecutive days in an out-patient setting. The treatment was repeated every 28 days for four cycles. Included were patients with a histological diagnosis of low grade NHL according to the Kiel classification and stage III or IV disease. Stage II patients were included when radiotherapy had failed. 55 patients were entered into the study. 50 patients were evaluable. The remission rate was 44/50 (88%; 95% confidence interval 82-100%), including complete remissions (CR) in 14 (28%) patients. Only 2 patients showed progression while on Cladribine treatment. The estimated overall survival, and time to treatment failure (TTF) were 85% and 51%, respectively, after a median observation time of 92 weeks. 11 (22%) patients showed grade 3 or 4 toxicity according to the WHO grading. Haematological toxicity was responsible for 86% of the overall toxicity and 100% of grade 3 and 4 toxicity. 7 patients (14%) had an infection, two of which were opportunistic. 12 (24%) patients did not experience any toxicity during the treatment. The results of this study clearly demonstrate the safety and considerable activity of this regimen. Cladribine is very effective even at lower doses than have been used so far.

Carboplatin, methotrexate and vinblastin (Carbo-MV) for advanced urothelial cancer. A phase II trial.

Fifteen patients with advanced urothelial cancer were treated with carboplatin 300 mg/m2, methotrexate 30 mg/m2, and vinblastin 3 mg/m2 on day 1 and the same dosage of methotrexate and vinblastin on days 15 and 22. Six patients were pretreated with radiotherapy and or chemotherapy; 7 patients had impaired renal function due to obstructive uropathy. Eight patients achieved a partial remission; 4 patients achieved a minor remission or stabilization of progressive disease. Mean duration of response was 8+ month (2+ to 12+ month). Subjective tolerance of the treatment was excellent but there was considerable bone marrow toxicity in the pretreated patients. The data show that Carbo-MV (carboplatin, methotrexate, and vinblastin) is effective and subjectively well tolerated in advanced urothelial carcinoma.

Extravasation of Oxaliplatin (Eloxatin((R))) - Clinical Course.

BACKGROUND: Up to now the cytostatic oxaliplatin was classified as nonvesicant. This is the first report on tissue necrosis induced by oxaliplatin extravasation in literature. A clinical course following oxaliplatin extravasation is reported. CASE REPORT: A 52-year-old white female with adenocarcinoma of the colon and hepatic and pulmonary metastases received palliative chemotherapy consisting of oxaliplatin, leucovorin, and 5-fluorouracil. By mistake oxaliplatin infusion extravasated subcutaneously in the left forearm; consequently, a painless red swelling occurred without any sign of further damage of the tissue. The infusion cannula was removed and oxaliplatin was infused into the right median cubital vein at the elbow. Again oxaliplatin extravasated subcutaneously. A severe painful necrotic reaction of the underlying flexor muscles of the right elbow developed, disabling the patient for 2 months, showing red-brown painful swelling, sclerosis of the skin, induration, fixation, and immobilization of the right elbow. Nonsteroidal analgesics and antibiotics were given, and lymphatic drainage and physiotherapy performed as generally accepted polypragmatic unspecific therapeutic procedure. After 2 months, the patient was able to bow and extend the right elbow except for an extension deficit of 20 degrees, pro- and supination became possible again, pain had completely resolved and strength recovered without limitation. Sclerosis of the skin and stiffness of the underlying tissue were slowly subsiding. CONCLUSION: Oxaliplatin can induce severe necrosis of underlying muscles by extravasation and therefore must be considered as a vesicant. Therefore oxaliplatin should be applied via a central venous access. Copyright 2000 S. Karger GmbH, Freiburg

[Spontaneous osteonecrosis of the knee joint in clinically suspected thrombosis of the leg veins]. / Spontane Osteonekrose am Kniegelenk bei klinischem Verdacht auf Beinvenenthrombose.

A case report demonstrating the value of X-ray examination in the diagnosis of spontaneous Osteonecrosis of the knee. The clinical, radiological and anatomic findings are pointed out and the differential diagnosis and therapeutic management are discussed.

Effective salvage therapy with carboplatin/mitomycin C in metastatic breast cancer.

BACKGROUND: Alternative and effective drug regimens in patients with metastatic breast cancer progressing after adriamycin- and taxoid-containing regimens are urgently needed. PATIENTS AND METHODS: In a phase II trial, 43 heavily pretreated patients with metastatic breast cancer were treated with both carboplatin 200 mg/m(2) i.v. and mitomycin C 10 mg/m(2) i.v. on day 1 every 4 weeks. In case of granulocytopenia or thrombocytopenia below grade 3 according to NCI-CTC, the carboplatin dosage was escalated to 300, 400, and 450 mg/m(2) in the next treatment cycle. RESULTS: During the first 3 cycles the dose intensity of carboplatin could be increased from a mean of 50 to 74 mg/m(2)/week. Beyond this value the carboplatin dose intensity decreased because of hematotoxicity. Based on an intention-to-treat analysis, 9 of 43 patients responded to therapy (21%; 95% CI = 10.04-36.04) including 2 complete and 7 partial responses. 15 patients had no change, 13 progressed, and 6 patients were considered nonevaluable. The median time to progression was 3 (range 0-12) months. NCI-CTC grade 3 or 4 granulocytopenia was observed in 14 patients, grade 3 or 4 thrombocytopenia occurred in 32, grade 3 infections in 3, grade 3 hemorrhage in 1, and grade 3 cardiac dysrhythmias in 1 of the patients. CONCLUSIONS: In anthracycline/ taxoid-pretreated patients, salvage treatment with a combination of carboplatin and mitomycin C seems to be effective and associated with foreseeable toxicity. Based on our results with an intraindividual dose escalation of carboplatin, a dosage of 300 mg/m(2) in combination with mitomycin C 10 mg/m(2) every 4 weeks seems to represent a recommendable starting dose for future studies.

[Pericarditis as the initial manifestation of retroperitoneal fibrosis--a case report]. / Perikarditis als Erstmanifestation einer Retroperitonealfibrose--ein Fallbericht.

HISTORY AND CLINICAL FINDINGS: A 70-year-old patient with invasive ductal breast cancer underwent conserving surgery of the right breast and right axillary dissection as well as postoperative irradiation therapy. Five months later, she presented with dyspnoea and progressive weakness. INVESTIGATIONS: Clinically, the patient showed anasarca and petechial hemorrhages, laboratory tests revealed thrombopenia, hepatic dysfunction, radiologic investigations showed enlargement of the liver and spleen, effusions of the pleura and pericardium, and ascite. Echocardiography showed pericardial effusion without cardiac tamponade. TREATMENT AND COURSE: Despite supportive therapy the patient's performance status deteriorated significantly, the diagnosis of the underlying disease could not be established, the patient died with the clinical signs of cardiovascular failure. Autopsy revealed progressive retroperitoneal fibrosis with systemic involvement of pleura, pericardium, epicardium, myocardium, lungs, and kidneys and pericarditis. Retrospectively clinical symptoms were interpreted as right heart insufficiency due to pericardial effusion. CONCLUSION: This case report reminds of occurrence of manyfold clinic manifestations of retroperitoneal fibrosis in dependence of particular organic involvement and that retroperitoneal fibrosis represents a differential diagnosis.

Recurrent granulocytic aplasia as clinical presentation of a persistent parvovirus B19 infection.

We report a case of persistent infection with human parvovirus B19 (PVB19), manifesting clinically as recurrent agranulocytosis and in bone marrow biopsy as recurrent pure granulocytic aplasia. Persistence of parvovirus infection was documented by the presence of PVB19 DNA and anti-PVB19-IgM antibodies in the serum for a period of 19 months. Granulocytic aplasia occurred only when anti-PVB19-IgG antibodies were not detectable in the serum and granulopoiesis showed immediate recovery with high dose intravenous immunoglobulin treatment. This case report suggests that the erythroid precursor cell may not be the only target cell of PVB19 infection. We suggest testing for active parvovirus infection in cases of aplasia of any lineage of the haematopoietic system.