PURPOSE: To review incidence and analyze profile of long-term complete responders among patients with undifferentiated carcinoma of nasopharyngeal type (UCNT) treated at a single institution. PATIENTS AND METHODS: We present a cohort of 20 long-term unmaintained complete responders to chemotherapy for metastatic UCNT treated at the Institut Gustave Roussy between April 1978 and November 1996. A patient was considered a long-term survivor if he or she was disease-free for more than 36 months without treatment after obtaining a complete response by chemotherapy. Patient characteristics were as follows: sex, 17 men and three women; median age, 28 years (range, 9 to 62 years); median World Health Organization performance status, 1; and initial tumor-node-metastasis stage (International Union Against Cancer–American Joint Committee on Cancer, 1987) of T3 to T4, 60%, and of N2b to N3, 75%. Epstein-Barr virus serology was characteristic in 19 patients. Of 16 pretreated patients, 11 were pretreated by radiotherapy alone and five by chemotherapy and radiotherapy. Thirteen patients had metastatic relapses of locally controlled UCNT. Tumor sites were bone in 15 patients, lung in four, and liver (biopsy-proven) in two. Chemotherapy included the following: cisplatin, bleomycin, and fluorouracil in five patients; bleomycin, epirubicin, and cisplatin in seven patients; fluorouracil, mitomycin, epirubicin, and cisplatin in four patients; and fluorouracil, bleomycin, epirubicin, and cisplatin in one patient. Three patients were treated with platinum-based regimens before 1985. Patients received a median of six cycles (range, three to 13). Thirteen patients with bone metastases received consolidating radiotherapy. RESULTS: As of June 1999, 14 of 20 patients were still alive with no evidence of disease after treatment (disease-free survival time, 82+ to 190+ months), three patients died of other causes while in complete response at 61, 109, and 208 months after treatment, and three patients died of disease at 42, 89, and 115 months after treatment. Long-term complete responses were obtained in both bone and visceral disease. CONCLUSION: Our data support a curative role for chemotherapy in metastatic UCNT and are a major incentive to continue research for better combinations to increase the percentage of patients with metastatic UCNT who attain complete responses and long-term survival.

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SUMMARYFew studies have analysed the antibody response during intravesical BCG immunotherapy for superficial bladder cancer. We have examined the evolution in serum antibody response against several heat shock proteins (hsp), including the recombinant mycobacterial hsp65 and the native protein P64 from BCG, GroEL from Escherichia coli (hsp60 family), recombinant mycobacterial hsp70 and the E. coli DnaK (hsp70 family), against purified protein derivative of tuberculin (PPD) and the AG85 complex of Mycobacterium bovis BCG, as well as against tetanus toxoid in 42 patients with a superficial bladder tumour, 28 treated with six intravesical BCG instillations and 14 patients used as controls. We also analysed the lymphoproliferative response of peripheral blood mononuclear cells against PPD in this population. Data of antibody responses at 6 weeks post BCG were available in all 28 patients,

The subcomponents of bacille Calmette‐Guérin (BCG) involved in the mechanism of action of intravesical BCG immunotherapy used for prophylaxis of superficial bladder cancer recurrences have been poorly investigated. We purified various BCG subcomponents and analyzed in vitro their ability to enhance a Th1 polarized immune response as well as to increase lymphocyte‐mediated cytotoxicity against bladder tumors. Human peripheral blood mononuclear cells (PBMCs) from healthy purified protein derivative–positive subjects were incubated for 7 days with whole BCG and various fractions (BCG cell wall, plasma membrane, cytosol, purified polysaccharides as glucan or arabinomannan, purified native proteins from BCG culture filtrate, recombinant 22 kDa protein, phosphate transporter PstS‐2 and ‐3 proteins). IFN‐γ, IL‐12, IL‐2, and IL‐6 production by stimulated PBMCs was compared to unstimulated controls and the phenotype of expanded cells analyzed by flow cytometry (FACS analysis). A 51Cr‐release assay monitored the cytotoxicity of amplified effector cells against T24 bladder tumor cells. Live BCG and most of its subcomponents (with the exception of cytosol, PstS‐2 and ‐3) significantly enhanced IFN‐γ and IL‐12 secretion, expanded CD3–CD56+ cells and the non‐MHC‐restricted cytotoxicity against bladder tumor cells compared to unstimulated controls (all P < 0.001, t‐test). IL‐2 receptor blockage resulted in a clear reduction in the cytotoxic activity of stimulated PBMCs. Numerous BCG subcomponents thus provide positive stimuli for Th1 cell differentiation and enhance in vitro, non‐MHC‐restricted cytotoxicity against bladder tumor cells. Our findings provide the basis for the therapeutic use of several of these subfractions in experimental animal models bearing bladder tumors. Int. J. Cancer 87:844–852, 2000. © 2000 Wiley‐Liss, Inc.

Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.

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Abstract:The central hypothesis of the collaboration between Language and Computing (L&C)