Recent advances in chemotherapy for advanced prostate cancer.

Recently, several important studies have validated prostate-specific antigen (PSA) as a reliable measure of response to chemotherapeutic treatment in advanced hormone-refractory prostate cancer. Furthermore, although chemotherapy in this setting has always been considered palliative, several analyses of recent clinical trials have demonstrated a significant association between declines in PSA values of 50% or more and prolonged survival. Mitoxantrone, in combination with prednisone, has been shown to provide significant palliation and improved quality of life. The use of combinations of chemotheraputic agents also seems to provide significantly superior objective and subjective responses compared with single-agent regimens. In particular, estramustine has been shown to synergize many of the agents used in prostate cancer treatment and has been demonstrated to provide significant palliation and decline in PSA levels in combination with vinblastine, vinorelbine, etoposide, paclitaxel, and docetaxel. The results of several important trials of the taxanes both as single agents and in combination with estramustine have been completed in the past year and have demonstrated that these agents are very effective in the treatment of hormone-refractory prostate cancer.

Extramural review of clinical response of breast cancer to cytotoxic chemotherapy.

Extramural evaluation of 385 clinical responses of advanced breast cancer agreed with the investigators' interpretation in 306 cases (79%) and disagreed in 19 cases (5%). Sixty cases (165%) were nonevaluable because of inadequate documentation. The rate of agreement with the seven groups of investigators ranged from 70% to 92%. The investigators had submitted their case material from review in preparation for their reporting on the relationship between the estrogen receptor content of breast cancer tissue and the response to cytotoxic chemotherapy. The reviewers used only objective criteria for their evaluation. They urge that clinical investigators report their findings quantitatively whenever possible and use standard methods of documentation.U

Relationship of quantitative estrogen-receptor level and clinical response to cytotoxic chemotherapy in advanced breast cancer. An extramural analysis.

Three hundred twenty-four patients with advanced breast cancer from seven institutions whose x-rays and records had been externally reviewed for evidence of objective regression of disease were again reviewed, this time regarding their responses to chemotherapy in relationship to estrogen receptor (ER) levels. Higher levels of ER were found in older or postmenopausal women, in those with longer disease-free intervals or with osseous metastasis, and in women whose chemotherapy treatment was given later relative to first recurrence of disease. Response to chemotherapy in 60%, or 194 cases, was comparable to the response rate in other patients treated with the same drugs. Patients with ER levels greater than 3 fmoles/mg cytosol protein had a response rate of 67% and 58% of patients with ER less than 3 fmoles responded. Regimens containing Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) in combination appeared to give higher response rates. Addition of vincristine or prednisone did not improve response rates. The best response rate (88%) was in 16 patients who had ER levels in excess of 50 fmoles and received four or more drugs. There appeared to be a benefit from increased number of drugs and from quantitatively high ER levels. There is a discussion of the possible implication of these findings.

The numb chin in breast cancer.

Numbness of the chin, an uncommon neurological symptom, was observed in 15 patients with cancer. Thirteen had breast cancer. This symptom usually heralded progressive involvement of the cranial nerves or cerebrum and denoted a poor prognosis in patients with a short `tumourfree interval'. The pathogenesis is commonly related to dural involvement of the Vth cranial nerve at the base of the brain, although metastasis to the mandible might sometimes be implicated. The reason for the peculiar predilection for the mandibular branch of the trigeminal nerve to be affected by breast cancer is not known.

Treatment of grade III and IV astrocytoma with dimethyl triazeno imidazole carboxamide (DTIC, NSC-45388) alone and in combination with CCNU (NSC-79037) or methyl CCNU (MeCCNU, NSC-95441).

The effectiveness of DTIC in the treatment of Grade III and IV astrocytomas was analyzed in two phases. In the first phase, 14 patients (Group A) with progressive neurologic dysfunction following primary treatment were treated with DTIC alone (8 patients) or in combination with CCNU or methyl CCNU (6 patients) and evaluated for change in neurologic status. Five of the 8 treated with DTIC responded symptomatically for a median duration of 18 weeks, and 3 of 6 treated with the combination of drugs responded for a median duration of 12 weeks. In the second phase, 15 patients (Group B) were treated within 4 weeks of surgical resection with radiation therapy and adjuvant chemotherapy with DTIC and/or MeCCNU. These patients were followed for survival and compared to a historical control group of 15 patients (Group C) treated with surgery and radiation only. The drug-treated group had a median survival of 55 weeks, compared to 35 weeks for the control group. Hematologic toxicity was life threatening in 2 of 14 patients treated with combination drugs, but mild with DTIC alone. DTIC appears to be active against malignant astrocytomas. Survival may be lengthened by combining chemotherapy with surgery and radiation therapy.