Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group

BACKGROUND: The aim of this trial was to compare the outcome achieved with neoadjuvant chemotherapy followed by radiotherapy to that achieved with radiotherapy alone for patients with locoregionally advanced undifferentiated or poorly differentiated nasopharyngeal carcinoma (NPC) meeting one of the following criteria: Ho's T3 disease, Ho's N2-N3 disease, or lymph node size > or =3 cm. METHODS: Between September 1989 and August 1993, 334 patients were enrolled in the study, with equal numbers of patients randomized to the neoadjuvant chemotherapy arm (CT arm) and the radiotherapy arm (RT arm). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (60 mg/m2 on Day 1) and epirubicin (110 mg/m2 on Day 1) followed by radiotherapy was given to the CT arm. For radiotherapy, a dose of 66-74 gray (Gy) (median, 71 Gy) was delivered to the primary tumor and 60-76 Gy (median, 66 Gy) to the neck. Two hundred eighty-six eligible patients completed the treatment and were evaluable for treatment response (134 in the CT arm, 152 in the RT arm). All patients were included in the survival analysis based on the intention to treat. The median follow-up was 30 months for the whole cohort and 41 months for the surviving patients. RESULTS: Analysis of the 334 patients based on the intention to treat showed no significant difference in relapse free survival (RFS) or overall survival (OS) between the 2 treatment arms (3-year RFS rate: 48% in the CT arm vs. 42% in the RT arm, P = 0.45; 3-year OS rate: 78% vs. 71%, P = 0.57). In an efficacy analysis based on only the 286 evaluable patients, a trend of improved RFS favoring the CT arm was observed (3-year RFS rate: 58% vs. 46%, P = 0.053), with again no significant difference in OS (3-year OS rate: 80% vs. 72%, P = 0.21). In the subgroup of 49 patients with bulky neck lymph nodes >6 cm, improved RFS (3-year RFS rate: 63% vs. 28%, P = 0.026) and OS (3-year OS rate: 73% vs. 37%, P = 0.057) were observed, favoring the CT arm. CONCLUSIONS: This multicenter randomized study did not demonstrate any benefit with the addition of cisplatin-epirubicin neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma; therefore routine administration of neoadjuvant chemotherapy to this target group cannot be recommended. Although the overall incidence of recurrence was reduced with the addition of chemotherapy in the efficacy analysis, the overall survival was not affected. A more effective chemotherapy regimen, the selection of an appropriate target group, and the use of an alternative strategy for combining chemoradiotherapy should be explored in future trials.     

The calretinin-containing mossy cells survive excitotoxic insult in the gerbil dentate gyrus. Comparison of excitotoxicity-induced neuropathological changes in the gerbil and rat

BACKGROUND: The locoregional failure rate remains high in advanced cervical carcinoma. Chemotherapy (CT) was added to radiotherapy (RT) in order to increase disease control and to improve 5-year survival. METHODS: CT + RT included cisplatin administered 100mg/m2, d.1 plus 5-fluorouracil 1000 mg/m2 D.1 to 5, ci (120 hrs), q every 3rd week for 3 cycles, followed by RT. RT included external beam irradiation 64.8 Gy in 1.8 Gy fractions, five days a week, by 4-field box technique. The median follow-up was 46 months. Ninety-four patients were evaluable for survival, 47 in the CT + RT group and 47 in the RT group. Ninety-two patients were evaluable for response. Known prognostic factors were equally distributed between the two groups. RESULTS: Of the 43 patients evaluable before RT, 31 (72%) achieved a partial or complete response after CT alone. After RT, 52 patients attained a complete response, 25 in the CT + RT group and 27 in the RT-group. Sixty-three patients developed distant metastases or local relapse, 30 in the CT + RT group and 33 in the RT group. In the CT + RT group 6 of the 9 patients with metastases also had local progression at relapse, in the RT group, 7 of 17 patients. The survival rates for the two groups are not statistically different. Thirty-seven patients are alive, 29 have no evidence of disease. Fifty-seven have died, 29 in the CT + RT group and 28 in the RT group. Fifty-four deaths were related to cancer, and 3 to therapy. CONCLUSIONS: Sequential CT and RT did not improve the survival, local control, or metastasis rate compared with RT alone.     

Pre-operative chemotherapy and radiotherapy in breast cancer

Primary systemic treatment of breast cancer with cytotoxics yields a high response rate and allows conservative surgical procedures in bulky tumours. In order to maximise local control of disease, two innovations were introduced in a pilot study. The first was to identify the good responders after three cycles of chemotherapy and to treat them with three additional cycles. The second was to also give this group of patients a full dose of radiotherapy before surgery with the aim of verifying the rate of pathological complete remissions in view of a possible treatment of breast primary with chemoradiotherapy only. Patients were treated with doxorubicin 60 mg/m2 and cyclophosphamide, 600 mg/m2 both intravenously on day 1, every 21 days for three courses. Partial or complete responders received three more courses followed by radiotherapy (50 Gy plus a 10 Gy boost). The others underwent immediate surgery. A total of 32 patients (median age, 50 years; range 28-69 years); performance status, 0-1; T2 22, T3 8, T4 2) were enrolled and were evaluable for response and side-effects. 9 patients had only three cycles of chemotherapy due to absence of response and 23 patients had six cycles of chemotherapy. Overall, 7 patients had a complete remission, 16 a partial remission and 9 had stable disease, for an overall response rate of 72% (95% confidence interval 53-86%). In the group of patients that completed the programme, two complete pathological remissions were observed and 5 patients had only microfoci of tumour. No toxic death or grade III-IV toxicities were observed. Mild or moderate side-effects included mucositis, nausea/vomiting and leucopenia. In conclusion, our results indicate that the addition of radiotherapy to pre-operative chemotherapy did not significantly enhance the incidence of pathological complete remissions. New primary treatment approaches should be explored in this subset of patients in order to improve outcome.     

Isolation, inoculation to insect host, and molecular phylogeny of an entomogenous fungus Paecilomyces tenuipes

BACKGROUND: To improve the poor prognosis of patients with advanced incurable gastric cancer, intensive chemotherapy combined with radical surgery was used. PATIENTS AND METHODS: Thirty patients with incurable gastric cancer were treated with a combination of 5-fluorouracil (370 mg/m2) and leucovorin (30 mg/person), given intravenously for five consecutive days, followed by cisplatinum (70 mg/m2) and etoposide (70 mg/m2) on days 6 and 20, delivered through a catheter placed either in the aorta with its tip at the level of the ninth thoracic vertebra or in the celiac artery. This treatment (FLEP therapy) was repeated twice every 5 weeks. Radical or palliative surgery followed chemotherapy. RESULTS: The overall response rate to the chemotherapy was 50.0% (15 of 30 patients, 95% confidence limit 0.305-0.671). Nineteen patients (15 with a partial response, three showing no change, and one with progressive disease) underwent surgery. Of these, nine underwent curative surgery and 10 palliative surgery. The median survival time was 6.5 months overall, 12.7 months for responders, and 4.7 months for nonresponders. Long-term survivors were exclusively found among patients with distant lymph node metastasis treated by curative surgery (55.6% at 5 years). CONCLUSIONS: Favorable results of this small phase II study justify a phase III trial.     

Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study

PURPOSE: Radiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided. PATIENTS AND METHODS: Patients received four cycles of carboplatin, etoposide, and bleomycin. Those with a complete response (CR) received two further cycles; others received two cycles intensified by cyclophosphamide. RESULTS: Seventy-one patients were enrolled (45 with germinoma and 26 with nongerminomatous GCT [NGGCT]). Sixty-eight were assessable for response. Thirty-nine of 68 (57%) achieved a CR within four cycles. Of 29 patients with less than a CR, 16 achieved CR with intensified chemotherapy or second surgery. Overall, 55 of 71 (78%) achieved a CR without irradiation. The CR rate was 84% for germinomas and 78% for NGGCT. With a median follow-up duration of 31 months, 28 of 71 patients were alive without relapse or progression. Thirty-five showed tumor recurrence (n = 28) or progression (n = 7) at a median of 13 months. Twenty-six of 28 patients (93%) who recurred following remission underwent successful salvage therapy. Pathology was the only variable predictive of survival. The probability of surviving 2 years was .84 for germinoma patients and .62 for NGGCT. Seven of 71 patients died of toxicity associated with study chemotherapy. CONCLUSION: Forty-one percent of surviving patients and 50% of all patients were treated successfully with chemotherapy only without irradiation. Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.     

Primary chemotherapy for stage 2 testis cancer

To evaluate the efficacy and toxicity of primary chemotherapy in patients with stage 2 (retroperitoneal lymph node metastases) testis cancer, 20 consecutive patients referred to Groote Schuur Hospital between September 1992 and March 1994 were reviewed. There were 10 patients with non-bulky non-seminomatous germ cell tumour (NSGCT), 5 with bulky NSGCT and 5 with bulky seminoma. The treatment regimen consisted initially of 4 cycles of cisplatin, etoposide and bleomycin. Patients with NSGCT and a residual mass after chemotherapy subsequently underwent retroperitoneal lymph node dissection (RPLND) and those with seminoma underwent a low dose of irradiation to the mass. In 7 (70%) of the 10 patients with non-bulky NSGCT, there was a complete response to chemotherapy and 3 patients underwent limited RPLND. One patient relapsed at follow-up but remains clear of disease after salvage therapy. The survival rate is 100% at a median follow-up of 60 months (range 12-143 months). In 5 patients with bulky NSGCT there was no complete response to chemotherapy. Three have undergone limited RPLND. The survival rate is 52% at a median follow-up of 130 months (range 108-152 months). In 5 patients with bulky seminomas, the survival rate is 100% at a median follow-up of 55 months (range 29-92 months). Toxicity has been modest except for 1 patient who died postoperatively in the early part of the study. Four patients have fathered children after treatment. We conclude that primary chemotherapy is the treatment of choice for patients with stage 2 testis cancer.     

Induction cisplatin/vinblastine and irradiation vs. irradiation in unresectable squamous cell lung cancer: failure patterns by cell type in RTOG 88-08/ECOG 4588. Radiation Therapy Oncology Group. Eastern Cooperative Oncology Group

PURPOSE: To analyze disease failure patterns by pretreatment characteristics and treatment groups in a prospective randomized trial. METHODS AND MATERIALS: Patients with medically inoperable Stage II, unresectable IIIA and IIIB nonsmall cell lung cancer with KPS > or =70 and weight loss < or =5% were randomized to one of three treatment groups: standard radiation therapy with 60 Gy at 2.0 Gy per day (STD RT), induction chemotherapy with cisplatin 100 mg/m2 days 1 and 29 with vinblastine 5 mg/m2 weekly for 5 weeks followed by 60 Gy at 2.0 Gy per day (CT + RT), or hyperfractionated radiation therapy with 69.6 Gy at 1.2 Gy b.i.d. (HFX RT). Of 490 patients enrolled, 458 were evaluable. Minimum and median periods of observation for this analysis were 4 years and 6 years, respectively. RESULTS: Pretreatment characteristics were equally distributed. Toxicities were previously reported. Median survival rates were 11.4, 13.6, and 12.3 months for STD RT, CT + RT, and HFX RT, respectively (log rank p = 0.05, Wilcoxon p = 0.04). Survivals were 20, 31, and 24% at 2 years, and 4, 11, and 9% at 4 years in the STD RT, CT + RT, and HFX RT groups, respectively. There were no differences in local tumor control rates among the treatments. Patterns of first failure showed less distant metastasis (DM) (other than brain) for CT + RT compared to the RT alone arms (p = 0.04). Within squamous cell carcinoma (SCC), DM (other than brain) rates were 43%, 16%, and 38% in SCC for STD RT, CT + RT, and HFX RT, respectively (p = 0.0015). Patients with peripheral/chest wall lesions were significantly more likely to fail first in the thorax when treated on STD RT compared to CT + RT and HFX RT (p = 0.009). Survival rates were similar among the treatment arms for patients with squamous cell carcinoma. Among patients with nonsquamous cell carcinoma, failure patterns did not differ by treatment group, but survival was significantly better in those who were treated by induction chemotherapy (p = 0.04). CONCLUSION: Patients with squamous cell carcinoma treated on the CT + RT arm had a significant reduction of first DM other than brain, but there was difference in survival. Survival favored CT + RT in nonsquamous carcinoma despite similar failure patterns. Reasons for improved survival with CT + RT in NSCLC are not yet available.     

Surgical outcomes of cataract extractions performed by residents using phacoemulsification

OBJECT: Although curative, radiation, which is conventionally administered for germinomas, causes significant neurological sequelae. This study aimed at reducing the volume and dose of radiation to a localized level of 24 Gy by pretreating the patient with chemotherapy. METHODS: Seventeen patients were divided into two risk groups based on serological findings and the extent of tumor. They were treated with chemotherapy prior to receiving localized radiation therapy. Six patients with solitary pure germinomas were treated with three or four cycles of cisplatin and etoposide (EP regimen) followed by 24-Gy local radiation therapy. Eleven patients with human chorionic gonadotropin (HCG)-secreting, multifocal, or disseminated germinomas received four to five cycles of ifosfamide, cisplatin, and etoposide (ICE regimen) followed by 24-Gy local radiation therapy. Craniospinal ports were used only in three cases of germinomas with dissemination. Gross-total resection was performed in three patients. Fourteen patients were able to be evaluated for their responses to chemotherapy. All patients achieved a complete response within three cycles. At a median follow-up duration of 24 months, 16 patients (94%) were alive without recurrence. One patient with an HCG-secreting germinoma experienced recurrence 38 months after surgery. That patient underwent successful salvage therapy using the same protocol. Thus, all 17 patients became free of disease with a 70 to 100% Karnofsky Performance Scale status. Toxicities associated with this study's chemotherapy regimen were mostly transient. No patient showed neurological or endocrinological deterioration during the follow-up period. CONCLUSIONS: The EP and ICE regimens were highly effective in treating the central nervous system germinomas and permitted dose and volume reduction of the radiotherapy. Localized 24-Gy irradiation was sufficient for disease control.     

Neoadjuvant combined therapy in stage IIIA if non-small-cell bronchial cancer

BACKGROUND AND OBJECTIVE: The overall prognosis of patients with stage IIIA non-small-cell lung cancer is unfavourable (median survival time 12 months). Tolerance to and efficacity of a multimodal neoadjuvant treatment was assessed in a prospective study. PATIENTS AND METHODS: 25 patients (median age 59 [37-69] years), with histologically confirmed mediastinal lymph node metastases, underwent chemotherapy. Immediately after two cycles with carboplatin/Ifosfamid (dimethoate)/etoposide they received hyperfractionated accelerated radiotherapy (45 Gy; 2 x 1.5 Gy daily) with simultaneous administration of carboplatin and vindesine. This was followed by tumour resection. RESULTS: After conclusion of the neoadjuvant treatment 19 of 25 patients (76%) had a remission. Of the 20 operated patients complete resection (R0) was possible in 17 (85%) and 14 of the 20 patients with resection (70%) had histologically demonstrated marked tumour regression. Critical toxicity consisted of pneumonitis and bronchial stump problems. Median survival time of all patients was 24.8 months and for patients with R0 resection 35.9 months. CONCLUSION: Neoadjuvant multimodal treatment of stage IIIA non-small-cell lung cancer can achieve prolongation in survival time. The place of radiotherapy or radiotherapy with chemotherapy in such a treatment concept will need to be defined in a randomized study.     

Sequential transurethral surgery, multiple drug chemotherapy and radiation therapy for invasive bladder carcinoma: initial report

Forty-seven patients with muscle-invasive bladder cancer (T2-T4, Nx, M0) were treated by transurethral resection, followed by 3-4 cycles of combination chemotherapy (methotrexate 30 mg/m2 on days 1, 14; cis-platinum 100 mg/m2 on day 2; vinblastine 3 mg/m2 on days 1, 14; repeated every 21 days), and external beam irradiation (64-66 Gy to the bladder and 40 Gy to the pelvic lymphatics). Complete remission after trans urethral resection and chemotherapy was achieved in 24 out of 45 patients (53%). Cystectomy was performed in patients without complete response to transurethral resection and chemotherapy. The therapy was completed as planned in 45/47 patients. After transurethral resection, chemotherapy, and radiation therapy, biopsy proven complete response was achieved in 62% (28/45); Stage T2T3 in 67% (23/34), Stage T4 in 45% (5/11) of patients. Among 19 patients with positive biopsy findings after transurethral resection and chemotherapy, 14 underwent cystectomy. After follow-up of 4-55 months (median 23 months) 75% (34/45) are alive, 68% (31/45) have had their bladders preserved, and 53% (24/45) are free of the primary tumor. The actuarial survival of all 45 patients is 73%. Moderate nausea and vomiting during treatment were common; severe leukopenia and mucositis were observed in five patients. Late side effects such as miction disorders and diarrhea were predominantly mild. Although the observation period has been too short to allow a definitive evaluation of treatment results, we feel both from the point of bladder preservation and disease-free survival that the presented treatment approach is successful in a majority of T2T3 patients, whereas a large tumor size (T4) renders this treatment less effective.     

Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma. Results of a prospective randomized study

BACKGROUND: In a prospective randomized manner, this study evaluated the effect of adjuvant chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; CHOP) in patients with Stage I non-Hodgkin lymphoma (NHL) who have achieved a complete response (CR) after radiation therapy (RT). METHODS: Forty-four patients with clinical or pathologic Stage I intermediate-grade or low-grade NHL were randomized to receive regional RT alone (median dose, 40 Gy) or regional RT followed by six cycles of CHOP chemotherapy. There were no differences in clinical and pathologic characteristics between the two treatment groups. RESULTS: The median follow-up was 7 years (range, 2-10 years). The actuarial relapse-free survival (RFS) rate for the RT plus CHOP group at 7 years was 83% compared with 47% (P < 0.03) for the RT-alone group. The overall survival (OS) for the two groups was 88% and 66%, respectively (P = 0.2). In patients with intermediate-grade NHL, the 7-year actuarial RFS for RT and CHOP was 86% compared with 20% for RT alone (P = 0.004). The corresponding actuarial survival rates were 92% and 47%, respectively (P = 0.08). In patients with low-grade histologic findings, the addition of adjuvant CHOP did not improve RFS (P = 0.6) or OS. All relapses in this study were at sites remote from the initially involved areas, and in 5 of 11 patients (45%), there were recurrences 5 years or longer after initial treatment. CONCLUSIONS: This study showed that adjuvant CHOP chemotherapy significantly improves RFS in patients with Stage I intermediate-grade NHL who achieve a CR after regional-field RT. The chemotherapeutic regimen favorably affected their probability of survival.     

Final report of a phase II study of chemotherapy with bleomycin, epirubicin, and cisplatin for locally advanced and metastatic/recurrent undifferentiated carcinoma of the nasopharyngeal type

PURPOSE: This article presents an assessment of the combination of bleomycin, epirubicin, and cisplatin as induction chemotherapy before radiotherapy in the treatment of undifferentiated carcinoma of the nasopharyngeal type in patients with recurrent/metastatic disease (group A), and in previously untreated patients with locoregionally advanced disease (UICC-AJCC 87, N2-3, M0) (group B) in terms of toxicity, antitumoral activity, and therapeutic efficacy. PATIENTS AND METHODS: From January 1987 to September 1990, 111 consecutive patients with histologically proven UCNT were treated with six cycles of intravenous cisplatin (100 mg/m2 day 1) epirubicin (80 mg/m2 day 1), and bleomycin (15 mg bolus day 1), followed by 16 mg/m2/day continuous infusion for 5 days, repeated every 21 days for three cycles. Three further cycles without bleomycin were given to 44 patients in group A. In group B (67 patients), only three cycles of the same protocol were given, with a slightly lower dose of epirubicin (70 mg/m2), followed by conventional radiotherapy (70 Gy/7 weeks). RESULTS: Of 44 patients entered in group A, 38 were evaluable for response. We observed 9 (20%) complete responses and 11 (25%) partial responses, for a 45% overall response rate. In 12 patients not previously given chemotherapy, there were 4 complete responses, compared to 5 complete responses in 32 patients previously treated with chemotherapy. Four patients are alive with no evidence of disease after 53+, 60+, 61+, and 72+ months. In group B the overall response rate to chemotherapy was 98% with 42 complete (62%) and 24 partial responses (36%). Three months after the end of radiotherapy, the overall complete response rate was 94% (63 patients). After a median follow-up time of 77 months (range, 53-94), the 4-year overall survival and disease-free survival rates for this group are 66% and 60%, respectively. The median disease-free survival has not been reached at 90 months. CONCLUSION: The results of the BEC combination trial are very encouraging in metastatic and recurrrent UCNT, with durable remissions in this poor-prognosis population. The results in patients with locally advanced disease have motivated prospective phase III testing of the neoadjuvant chemotherapy approach to evaluate its impact on locoregionally advanced disease (> or =N2MO UICC-AJCC 87).     

Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study

OBJECTIVE: Induction chemoradiotherapy followed by surgery may improve survival rates among patients with esophageal carcinoma. We designed a novel intense induction regimen with paclitaxel and high-dose hyperfractionated radiotherapy to maximize complete response rates. METHODS: Forty patients with esophageal cancer were treated in a phase I and II trial of induction chemotherapy (cisplatin, 5-fluorouracil, and paclitaxel) at three dosage levels (75, 125, and 100 mg/m2) and concurrent hyperfractionated radiotherapy (45 Gy to the mediastinum, 58.5 Gy to the tumor). The mean age was 62 years, and 32 patients (80%) had adenocarcinoma. Twenty-eight of 40 (70%) patients had locally advanced tumors (T3, or stage IIB or greater). RESULTS: The average hospitalization for induction treatment was 17 days. Toxicity was substantial, with esophagitis necessitating nutritional support the most common complication. The maximum tolerated dose of paclitaxel was 100 mg/m2. Two patients died during induction treatment. Thirty-six patients (90%) underwent resection. The median length of stay was 10 days, and two patients died after the operation. Fourteen of 36 patients (39%) had a pathologic complete response. Patients who received all prescribed chemotherapy had a higher pathologic complete response rate (50%) than did patients who required dose reduction (17%; p = 0.076). The 2-year survival rate was 61% (95% CI 35% to 86%) with a median follow-up of 11.9 months. CONCLUSIONS: Paclitaxel at a dose of 100 mg/m2 appears to have acceptable toxicity. The high pathologic complete response rate in this regimen is encouraging, but it is associated with substantial toxicity. The toxicity of this regimen is not acceptable and will require substantial reduction in the radiation component. Survival data are too short-term to confirm enhanced survival.     

Primary chemoradiation therapy with fluorouracil and cisplatin for cancer of the anus: results in 35 consecutive patients

PURPOSE: This prospective phase II study was designed to test the activity and toxicity of a regimen of fluorouracil (5-FU) and cisplatin (CDDP) in combination with radiation therapy in the treatment of epidermoid cancer of the anal canal. PATIENTS AND METHODS: Thirty-five consecutive patients with untreated epidermoid cancer of the anal canal were candidates for chemoradiation therapy (CRT). Staging of cancer was as follows: T1, 26%; T2, 60%; T3, 14%; and N1, 2,3, 26%. No patient had distant metastases. The treatment protocol consisted of two to three cycles of chemotherapy starting on days 1 and 21 and concurrent radiotherapy at a daily dose of 1.8 Gy up to a total dose of 36 to 38 Gy in 4 weeks, delivered to the anal region, perineum, middle and lower pelvis, and inguinal and external iliac nodes. Radiotherapy was then delivered to the anoperineal region and metastatic inguinal nodes to a total dose of 18 to 24 Gy in 10 fractions. Chemotherapy consisted of 24-hour intravenous (IV) infusion of 5-FU 750 mg/m2 on days 1 to 4 and CDDP 100 mg/m2 by 60-minute IV infusion on day 1. RESULTS: All patients received two cycles of chemotherapy; the second was delayed in three patients because of leukopenia that was evident in 11 (31%). In eight patients, a third cycle was added. They all experienced nausea or vomiting; one patient showed signs of cardiotoxicity and one developed proctitis, dermatitis, and diarrhea (grade 3). Complete regression (CR) was assessed in 33 patients (94%); nine patients with metastatic lymph nodes also had CR. Two patients had a partial response (PR); both underwent abdominoperineal resection, which was not curative in one. Two patients (6%) had a local recurrence; in one, this was associated with hepatic metastases. One of these patients underwent surgery and is alive after about 4 years, while the other is undergoing chemotherapy. After a median follow-up duration of 37 months, 94% of patients are alive without evidence of disease and 86% are colostomy-free. CONCLUSION: This regimen is well tolerated; its toxicity does not exceed that observed with the combination of 5-FU and mitomycin (MMC). Compared with our previous experience based on the classic CRT (5-FU, MMC, and radiation), the objective response rate observed with this new combination was similar. However, the local recurrence rate, observed in patients treated with the new regimen, was lower (6% v 24%). According to more recent data from the literature, primary CRT is the elective indication in epidermoid cancer of the anus and replacement of MMC with CDDP seems an effective and logical evolution.     

Induction chemotherapy followed by concurrent chemoradiation for advanced head and neck cancer: improved disease control and survival

PURPOSE: To determine tumor response rate, patterns of failure, toxicity, and survival in advanced squamous head and neck cancer after a combined treatment program that consists of induction chemotherapy, organ-sparing surgery, and concurrent chemoradiation. Long-term outcome data are presented. PATIENTS AND METHODS: Between July 1991 and March 1993, 93 patients received three cycles of induction chemotherapy that consisted of cisplatin, fluorouracil (5-FU), l-leucovorin, and alpha-interferon2b (PFLl-alpha) followed by optional limited surgery and six to eight cycles of 5-FU, hydroxyurea, and concurrent radiation (FHX) to a total radiation dose of 65 to 75 Gy. RESULTS: Ninety-three patients were entered onto this study and 97% had stage IV disease, with 66 patients who were N2 or N3. Sixty-one patients (66%) achieved a clinical complete remission (CR) after induction therapy. Thirty-four patients underwent surgery. Seventy-nine patients proceeded to FHX. With a median follow-up time of 43 months for surviving patients, 20 patients have had disease progression (13 local, two distant, five both), and there have been 35 deaths (18 from disease, six treatment-related, two from a second primary, and nine for other medical reasons). At 5 years, progression-free survival is 68%, and overall survival is 62%. Surgery was organ-preserving, as only a single laryngectomy and no glossectomies were performed in primary management. Acute toxicity related to PFLl-alpha consisted of severe or life-threatening mucositis in 57% and leucopenia in 65% of patients. During FHX, 81% of patients had grade 3 or 4 mucositis. CONCLUSION: PFLl-alpha is a highly active regimen that induced clinical CR in two thirds of patients. When followed by limited surgery and FHX, resultant local and distant disease control, organ preservation, and overall 5-year survival are very promising in high-risk stage IV patients. Based on these local control and survival data, further evaluation of this treatment sequence, induction chemotherapy followed by concurrent chemoradiation, is warranted. Identification of similarly active but less toxic regimens is a high priority.     

Pharmacokinetics of CDDP by the route of administration in patients with ovarian cancer

Seventy patients with local squamous cell carcinoma of the esophagus were treated between 1981 and 1990 with preoperative chemotherapy, surgical resection, and possible postoperative radiation therapy and/or chemotherapy. Chemotherapy included two cycles of 5-fluorouracil (1000 mg/m2) by continuous intravenous infusion on days 1-4 and cisplatin (100 mg/m2) on day 4. Complete clinical response (CCR) was achieved in 28 (41%) patients, partial clinical response (PCR) in 17 (25%), and no response in 23 (34%). Fifty-five (81%) patients were resected, 6 (9%) were explored, and 7 (10%) were unable to have surgery. Microscopic analysis of 55 resected patients showed 50 (91%) with active tumor, 1 (2%) with necrotic tumor, and 4 (7%) with a pathological complete response to chemotherapy. Twenty-six of the 55 resected patients (47%) had no gross evidence of disease at the time of surgical inspection. Median overall survival was 21.86 months (range 2-107 months) for all patients and 26.71 months (range 2-107 months) for resected patients. Actuarial 5-year survival rate was 31% for all patients and 39% for resected patients. Prolonged survival correlates with complete clinical response to chemotherapy, low pathological stage of disease, and successful resection of the lesion.     

Treatment and prognosis in a series of primary extranodal lymphomas of the ocular adnexa

BACKGROUND: The aim of this study was to assess clinicopathological characteristics and outcome in a series of primary ocular adnexal lymphomas (POALs). PATIENTS AND METHODS: Nineteen patients with localised (stage IE) POAL were followed for a median of 96 months (24-156). The diagnosis was based on surgical biopsies followed by immunohistochemistry in 16 cases or fine-needle aspiration followed by immunocytophenotypic analysis in three cases. Twelve patients were treated with local radiotherapy (RT), five with chemotherapy (CT), and two refused further therapy after apparently radical tumour removal achieved by the diagnostic excisional biopsy. RESULTS: The histological and immunological pattern was consistent with a diagnosis of MALT-type lymphoma (11 cases), follicular center non-Hodgkin's lymphoma (three cases). a large-cell variant of Burkitt's lymphoma (one case), and large-cell transformed MALT lymphoma (one case). Low-grade lymphoma was diagnosed in the three cases which underwent fine-needle aspiration biopsy. All of the patients achieved and maintained complete remission except for those treated with surgical excision alone (two MALT conjunctival lymphoma cases): one of these relapsed locally, the other experienced the systemic spread of a transformed diffuse large-cell lymphoma and died 72 months after diagnosis. The side effects consisted of two cases of RT-related cataract after 52 and 72 months. CONCLUSIONS: Regardless of histology, prognosis was excellent when surgery plus RT was adopted, and CT seems to be a valid alternative to RT. Surgery alone may be sub-optimal.     

Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03

PURPOSE: To assess the efficacy of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy in patients with muscle-invading bladder cancer treated with selective bladder preservation. PATIENTS AND METHODS: One hundred twenty-three eligible patients with tumor, node, metastasis system clinical stage T2 to T4aNXMO bladder cancer were randomized to receive (arm 1, n=61 ) two cycles of MCV before 39.6-Gy pelvic irradiation with concurrent cisplatin 100 mg/m2 for two courses 3 weeks apart. Patients assigned to arm 2 (n=62) did not receive MCV before concurrent cisplatin and radiation therapy. Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. The CR patients were treated with an additional 25.2 Gy to a total of 64.8 Gy and one additional dose of cisplatin. Those with less than a CR underwent cystectomy. The median follow-up of all patients who survived is 60 months. RESULTS: Seventy-four percent of the patients completed the protocol with, at most, minor deviations; 67% on arm 1 and 81% on arm 2. The actuarial 5-year overall survival rate was 49%; 48% in arm 1 and 49% in arm 2. Thirty-five percent of the patients had evidence of distant metastases at 5 years; 33% in arm 1 and 39% in arm 2. The 5-year survival rate with a functioning bladder was 38%, 36% in arm 1 and 40% in arm 2. None of these differences are statistically significant. CONCLUSION: Two cycles of MCV neoadjuvant chemotherapy were not shown to increase the rate of CR over that achieved with our standard induction therapy or to increase freedom from metastatic disease. There was no impact on 5-year overall survival.     

A novel zinc finger cDNA with a polymorphic pentanucleotide repeat (ATTTT)n maps on human chromosome 19p

PURPOSE: To evaluate the therapeutic effectiveness of a combined chemoradiotherapy program, followed by surgery in selected cases, in Stage III non-small cell lung cancer. METHODS AND MATERIALS: Between August 1988 and February 1990, 43 patients Staged IIIa-b (UICC 1987, 58% IIIb) have been treated with concomitant chemotherapy (cisplatin 15 mg/m2 and VP16 75 mg/m2, 5 days a week on week 1 and 5) and radiotherapy (40 Gy split course, 2 Gy/day on week 1, 2, 5, and 6), followed by attempted curative thoracotomy or more cycles of full dose chemotherapy with the same two drugs. RESULTS: Planned chemoradiotherapy has been given to 91% of patients; 13/43 patients have been operated, with 12 complete resections and three (7%) pathological complete responses. Toxicity was significant, with two postoperative deaths and two fatal radiation pneumonitis. Crude progression-free survival rate is 21% at 30 months, with nine patients (21%) alive and free from progression at follow-up times ranging from 31 to 49 months. Subset survival analysis showed a possibly greater therapeutic effect for non-squamous histology as compared to squamous carcinoma. CONCLUSION: These results are encouraging in a cohort of patients with quite advanced disease (58% Stage IIIb).     

No association between particular DRD3 and DAT gene polymorphisms and manic-depressive illness in a Spanish sample

Cisplatin-based chemotherapy is highly effective in non-seminomatous testicular cancer. Patients with advanced disease receive two to four cycles of polychemotherapy. Residual retroperitoneal masses after chemotherapy are suspected to contain active tumour tissue as well as mature teratoma. Therefore, a delayed retroperitoneal lymph node dissection remains necessary. A total of 123 patients with advanced non-seminomatous germ cell cancer underwent retroperitoneal surgery after two different regimes of cisplatin-based chemotherapy. The first group (n = 55) received a sequential alternating chemotherapy with Adriamycin/cisplatin and bleomycin/vinblastine (8.5 +/- 5 cycles, 1979-1985), the second group (n = 60) got a standard PEB scheme (cisplatinum /etoposide/bleomycin; 5.7 +/- 2.1 cycles, 1985-1991). Eight patients got other cisplatin-based combinations. All patients received adjunctive retroperitoneal surgery. After a mean follow-up period of 72 months, the patients treated with the sequential alternating scheme showed a survival rate of 50% (27/54, 1 patient lost to follow-up). After the PEB scheme a survival rate of 79% (46/58, 2 patients lost to follow-up) was found. 86% of the patients with retroperitoneal necrosis after retroperitoneal lymph node dissection (RPLND; n = 58) survived with no evidence of disease, as well as 82% of the patients with adult teratoma (n = 18). Only 47% of the patients with residual active carcinoma after RPLND (n = 47) survived within a follow-up period of (median) 72 months, despite further chemotherapy after RPLND. Residual tumor burden and type of histology after RPLND can partially predict the clinical outcome. A necrotic specimen in RPLND could not be predicted by any means, so that surgical removal of a residual retroperitoneal mass after chemotherapy remains necessary. Standard PEB chemotherapy is superior to sequential alternating chemotherapy.