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Lessons Learned Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate. This phase II study did not meet its primary endpoint. Cabazitaxel has low activity in SCCHN. The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%). Background. Cabazitaxel is a second-generation taxane that improves the survival of patients with metastatic castrate-resistant prostate cancer following docetaxel therapy. Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. In this randomized phase II trial, we investigated cabazitaxel in patients with recurrent SCCHN. Methods. Patients with incurable SCCHN with progression after platinum-based therapy were randomly assigned to cabazitaxel every 3 weeks (cycle 1, 20 mg/m2, increased to 25 mg/m2 for subsequent cycles in the absence of nonhematological adverse events [AEs] greater than grade 2 and hematological AEs greater than grade 3) or methotrexate (40 mg/m2/week). The patients were stratified according to their performance status and previous platinum-based chemotherapy for palliation versus curative intent. The primary endpoint was the progression-free survival rate (PFSR) at 18 weeks. Results. Of the 101 patients, 53 and 48, with a median age of 58.0 years (range, 41–80), were randomly assigned to cabazitaxel or methotrexate, respectively. The PFSR at 18 weeks was 13.2% (95% confidence interval [CI], 5%–25%) for cabazitaxel and 8.3% (95% CI, 2%–20%) for methotrexate. The median progression-free survival was 1.9 months in both arms. The median overall survival was 5.0 and 3.6 months for cabazitaxel and methotrexate, respectively. More patients experienced serious adverse events with cabazitaxel than with methotrexate (54% vs. 36%). The most common drug-related grade 3–4 AE in the cabazitaxel arm was febrile neutropenia (17.3%). Conclusion. This study did not meet its primary endpoint. Cabazitaxel has low activity in recurrent SCCHN.

INTRODUCTION: We report here two cases of Agrobacterium radiobacter bacteremia. These cases were observed at the same institution over a short time period (3 months). CASE REPORTS: The first patient was a female cancer patient receiving third-line chemotherapy for ovarian carcinoma. When she developed bacteremia, she was neutropenic and had an indwelling catheter that was removed as part of the treatment. The second case was a geriatric patient admitted from home with bacteremia, clinical signs of septic shock, and concomitant acute cholecystitis. OUTCOME: Both patients responded promptly and completely to antibiotherapy. No recurrence was observed.

Tumor infiltrating lymphocytes (TIL) display activation markers and their presence is often associated with a favorable outcome. The role of tumor antigens in T cell recruitment into tumors is unclear. In an attempt to address this issue, we purified lymphocytes from breast tumor or nontumor, mammary tissue from patients, and normal mammary tissue from healthy individuals. In all groups, including healthy individuals, the majority of cells displayed an effector/memory (CD45RA lo /CD27 1/2 ) phenotype and quite surprisingly the early and transient activation marker CD69, thus, questioning the tumor antigen specificity of TIL. Because the human repertoire is diverse, the T cells found in the tumors could recognize both self/tumor and environmental antigens through cross-reactivity. To test this hypothesis, we used two anti-male HY monospecific TCR transgenic mouse models. We found an infiltration of HY negative tumors by the CD4 1 and CD8 1 monoclonal T cells after priming with HY positive cells in the periphery. Thus, the presence of activated effector/memory T lymphocytes in tumors can be independent of reactivity against tumor antigens. These results suggest that to find activated effector T cells in a tissue does not always mean that a specific immune response is taking place. ' 2005 Wiley-Liss, Inc.

The cancer-germline gene MAGE-3 codes for tumor-specific antigens recognized on many tumors by T lymphocytes. A MAGE-3 antigen presented by HLA-A1 has been used in several vaccination trials on metastatic melanoma patients. Only a small minority of patients have shown evidence of tumor regression. Attempts to correlate the tumor rejections with the cytotoxic T lymphocyte (CTL) response against the vaccine have been hampered by the low level of these responses. In noncancerous individuals, the frequency of the T cell precursors against antigen MAGE-3.A1 is ≈4 × 10 -7 CD8 T cells. The diversity of the T cell receptor repertoire of these anti-MAGE-3.A1 precursors was analyzed in one individual. The results indicate that it is very likely that the repertoire comprises >100 clonotypes. On this basis, it is possible to use not only the frequency of CTL precursors in the blood but also the presence of dominant clonotypes to ascertain in patients the existence of anti-MAGE-3.A1 responses as low as 10 -6 of CD8. With this approach, we observed a correlation between tumor regression and anti-MAGE-3.A1 CTL responses in patients vaccinated with a recombinant virus encoding the antigen and also in patients vaccinated with peptide-pulsed dendritic cells. In contrast, for patients showing tumor regression after vaccination with peptide alone, CTL responses were almost never observed. It is possible that even those CTL responses that are below our present detection level can trigger a sequence of events that leads to tumor regression.

'Cancer-germline' genes such as the MAGE gene family are expressed in many tumors and in male germline cells but not in normal tissues. They encode shared tumor-specific antigens, which have been used in therapeutic vaccination trials of metastatic melanoma patients. To establish whether there is a correlation between tumoral regressions and T-cell responses against the vaccine antigen, we evaluated the responses of patients vaccinated with a MAGE-3 antigenic peptide or a recombinant virus coding for the peptide. Blood lymphocytes were stimulated with antigenic peptide followed by detection with tetramer, T-cell cloning, and TCR analysis. In 4/9 regressor patients and in 1/14 progressors we found a low level, usually monoclonal cytolytic T lymphocyte response against the MAGE-3 peptide.