Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: results of single-center study of 45 patients.

BACKGROUND: Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation. METHODS: We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment. RESULTS: The mean age was 56.6 years (range, 34-75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis. CONCLUSION: Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival.

Salvage ifosfamide-doxorubicin chemotherapy in patients with recurrent nasopharyngeal carcinoma pretreated with Cisplatin-based chemotherapy.

This study evaluated the efficacy and toxicity of ifosfamide and doxorubicin chemotherapy regimen in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Twenty-one patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy as adjuvant or palliative treatments who received ifosfamide 2500 mg/m(2) d 1-3, mesna 2500 mg/m(2) d 1-3, doxorubicin 60 mg/m(2) d 1, repeated every 21 d was retrospectively analyzed. Patients received a median number of three cycles of ifosfamide-doxorubicin (range: 1-6). Seven patients (33.3%) achieved partial response and no patient achieved complete response. Six (28.5%) had stable disease, whereas three (18.75%) had progressive disease. The median time to progression was 7.0 mo. Ifosfamide-doxorubicin regimen is an effective salvage regimen in patients with recurrent and metastatic NPC.

Calcium and vitamin D supplementation during bisphosphonate administration may increase osteoclastic activity in patients with bone metastasis.

Bone metastasis are a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer. The consequences of bone metastasis are often devastating. Osteolytic metastasis can cause different kinds of skeletal related events including severe pain, pathologic fractures, life-threatening hypercalcemia, spinal cord compression, and other nerve-compression syndromes. These skeletal-related events are the result of the resorption of mineralized bone by osteoclasts. Bisphosphonates are synthetic analogues of naturally occurring pyrophosphate compounds that inhibit bone resorption. Potent bisphosphonates, pamidronate and, more importantly zoledronic acid may cause hypocalcemia, but mostly asymptomatic, mild, transient in most cases. Sufficient calcium and vitamin D intake needs to be ensured in patients with malignancy who have borderline or low levels of calcium when commencing treatment with bisphosphonates. Vitamin D itself induce the formation of osteoclasts by increasing the expression of RANKL on marrow stromal cells. Local calcium also promotes tumor growth and the production of parathyroid hormone-related peptide which in turn stimulates bone resorption. Vitamin D and calcium supplementation during bisphosphonate administration for the purpose of elimination of the side effects related to hypocalcemia in patients with bone metastasis may increase the bone resorption and decrease the efficacy of bisphosphonates. Therefore, vitamin D and calcium supplementation must not be routinely recommended during bisphosphonate administration.

Hypocalcemic effect of zoledronic acid or other bisphosphonates may contribute to their antiangiogenic properties.

Bisphosphonates, effectively used for metastatic bone disease and hypercalcemia, may evidentially have antiangiogenic properties. However, mechanism(s) of antiangiogenic effects of bisphosphonates are not fully understood. Their most pronounced effect is on metabolism of calcium, which is a main point of intersection for many distinct molecular signaling pathways that promote and modulate angiogenesis. An elevation of Ca(2+) plays a role in the mitogenic and secretory effects of growth factors. Some preclinical clues imply that antiangiogenic effects of bisphosphonates are related to its well-known hypocalcemic activity. Consequently, it may not be right to routinely recommend vitamin D and calcium supplementation to correct hypocalcemia unless it is symptomatic.

Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists.

Angiogenesis, cellular growth and invasion of a cancer cell are attractive targets for new treatment strategies of malignancies in recent years. The evidences are accumulating that ACE inhibitors and angiotensin II type 1 antagonists could be novel anti-angiogenic, anti-invasive, and even anti-growth agents against neoplastic tissues: The renin-angiotensin system promotes angiogenesis directly or indirectly and growth of neoplastic cell. Some tumors carry angiotensin II type 1 receptors. Angiotensin II antagonists and angiotensin-I-converting enzyme inhibitors have shown some anti-neoplastic actions. Angiotensin II receptor blocker losartan antagonises platelets, which are thought to modulate via vascular endothelial growth factor. They may even protect the patient from the major toxicity of chemotherapy and/or radiotherapy, myelotoxicity, enabling us to give higher doses and end up with higher success rate. We believe that these agents can be useful on clinical grounds and suggest their incorporation into clinical studies.