Disseminated neuroblastoma in children older than one year at diagnosis: comparable results with three consecutive high-dose protocols adopted by the Italian Co-Operative Group for Neuroblastoma.

PURPOSE: To compare the outcomes associated with modifications in three consecutive protocols employed by the Italian Co-Operative Group for Neuroblastoma (ICGNB) in disseminated neuroblastoma. PATIENTS AND METHODS: Between January 1985 and November 1997, a total of 359 children aged 1 to 15 years with newly diagnosed stage 4 neuroblastoma were enrolled in three consecutive protocols. Compared with ICGNB-85, the ICGNB-89 protocol contained two more chemotherapy cycles, and some drugs were given at greater doses, whereas in the ICGNB-92 protocol, the induction phase included a chelating agent, and individual cycles contained four drugs instead of two. RESULTS: A total of 330 of 359 evaluable children were included in this analysis; 106 children were treated with ICGNB-85, 65 children were treated with ICGNB-89, and 159 children were treated with ICGNB-92 protocols. Radical resection of primary tumor was carried out in 59.4%, 50.8%, and 57.9% of the patients, respectively. Major tumor response after induction therapy was achieved in 66.7%, 69.2%, and 68.6% of the patients, respectively. A total of 218 of 232 patients received consolidation therapy consisting of conventional chemotherapy in 65 patients and of high-dose chemotherapy in 153 patients. Disease recurrence or progression occurred in 82.1%, 69.2%, and 74.8% of the patients, respectively. Therapy-related deaths occurred in 1.9%, 12.3%, and 6.9% of the patients, respectively. Five-year overall survival (OS) for the three studies was 26%, 23%, and 28%, and event-free survival (EFS) was 19%, 17%, and 17%, respectively. CONCLUSION: The therapeutic modifications adopted in the ICGNB-89 and ICGNB-92 protocols were not associated with a significant improvement in response rate or in the 5-year OS and EFS as compared with the ICGNB-85 protocol. Attempts at intensifying chemotherapy were associated with greater toxicity.

Response to first-line chemotherapy and long-term survival in patients with multiple myeloma: results of the MM87 prospective randomised protocol.

In this study we evaluated whether a good response to conventional chemotherapy, i.e. a significant tumour reduction, is a prerequisite for improved survival in multiple myeloma (MM). Between January 1987 and March 1990, 341 consecutive previously untreated patients with MM received chemotherapy within the prospective, multicentre, randomised Protocol MM87. Of these, 258 patients were evaluable for both response and long-term survival and 244 (94.6%) have died. The median survival of all patients was 40 months (6-162 months). The median survival did not differ between patients who had complete response (CR) (50 months (9-162 months)), partial response (PR) (46 months (8-147 months)) or stable disease (SD) (41 months (7-135 months)). The median survival was shorter (13.6 months (6-135 months)) (P<0.0001) in patients whose disease progressed while they were receiving first induction chemotherapy. Causes of death were more frequently (P=0.04) related to MM in patients who had progressive disease (PD) than in patients who had a CR or PR or SD. The main clinical and laboratory characteristics were similar in the four groups. These data indicate that patients who maintain SD during first-line chemotherapy have a prognosis similar to that of patients who attain a response. Only patients whose disease progresses have a distinctly worse outcome.

An observation on combined use of chemotherapy and traditional Chinese medicine to relieve cancer pain.

We have treated 50 patients with stage III, VI malignant tumors confirmed by pathology. The patients were divided into two groups. One group was treated by combination of chemotherapy and traditional Chinese medicine (treatment group); the other only by chemotherapy (control group). The effect of cancer treatment was evaluated according to the criteria of WHO. The results showed that the effective rate was 80% in treatment group and 52% in control group. The pain relieving rate was 68% in treatment group and 40% in control group (P < 0.01). This fact demonstrates that the application of traditional Chinese medicine can invigorate blood circulation, eliminate blood stasis, soften hardness and dissolve the mass, nourish blood and increase vigor. This kind of application can not only enhance the effect of cancer treatment but also increase the cancer pain relieving rate.

Experience with poorly myelosuppressive chemotherapy schedules for advanced myeloma. The Cooperative Group of Study and Treatment of Multiple Myeloma.

In a multicentre study, 83 patients with advanced and previously uniformly treated multiple myeloma (MM) were randomised between cyclophosphamide (600 mg m-2) and epirubicin (70 mg m-2), administered every 3 weeks for three courses and both associated with prednisone and interferon-alpha2b. Both regimens were administered on an outpatient basis and had low haematological toxicity. Clinical results were similar. Overall response rate (43%) and median response and survival (5.9 and 14.1 months respectively) compare well with those obtained with more aggressive chemotherapy schedules.

Effect of alternating combination chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide for small cell lung cancer on hematopoietic progenitors in the peripheral blood.

The effects of a combination chemotherapy (CAV-PVP) consisting of cyclophosphamide, doxorubicin, hydrochloride (dox) and vincristine (CAV) alternating with cisplatin and etoposide (PVP) on peripheral blood hematopoietic progenitor cells (PBHPs) were studied in five patients with small cell lung cancer (SCLC). The kinetics of the CFU-GM levels were different during the CAV and PVP phases. None of the five patients displayed a rebound increase in the level of peripheral blood CFU-GM during the CAV phase. In contrast, all five patients displayed a rebound increase in peripheral blood CFU-GM levels during the PVP phase of the alternative combination chemotherapy (3-5 weeks after the initiation of PVP regimen). These findings indicate the optimal timing for leukapheresis to obtain PBHPs in SCLC patients which have been treated with an alternating combination chemotherapy consisting of CAV-PVP.

Standard-dose and high-dose peptichemio and cisplatin in children with disseminated poor-risk neuroblastoma: two studies by the Italian Cooperative Group for Neuroblastoma.

PURPOSE: The objective of the present study was to determine whether an increase in the intensity of therapy improves outcome for children with disseminated poor-risk neuroblastoma. PATIENTS AND METHODS: From January 1982 through November 1989, 181 children 1 year or older with newly diagnosed disseminated neuroblastoma were entered onto two consecutive studies of the Italian Cooperative Group for Neuroblastoma (ICGNB): 75 (study NB82) were enrolled from 1982 to 1984 and were treated with standard-dose (SD) chemotherapy, and 106 (study NB85) were enrolled from 1985 to 1989 and received high-dose (HD) chemotherapy. In both treatment protocols, induction therapy included peptichemio and cisplatin (at SD or HD, respectively) and removal of the primary tumor. In study NB82, children who achieved complete or partial tumor regression received SD consolidation therapy, and in study NB85 they received three cycles of HD chemotherapy (3cCT) or one cycle of myeloablative therapy (MAT) followed by autologous bone marrow transplantation (ABMT). RESULTS: Compared with group NB82, the NB85 group had significantly fewer failures (no tumor response or disease progression) after administration of peptichemio (9% v 31%; P < .01), had more complete responses (CRs) and partial responses (PRs) both after treatment with cisplatin (60% v 43%; P = .01) and after surgery (76% v 57%; P < .01), and was more likely to have achieved complete excision of the primary tumor (70% v 46%; P < .01). Overall survival (OS) and progression-free survival (PFS) at 5 years were 11% and 9% in NB82, and 27% and 18% in NB85 (P < .01 for both); however, in NB85, relapses occurred even after 5 years of CR, so that PFS curves converge approximately 7 years after diagnosis. Median survival time was 14 months in NB82 and 24 months in NB85. Children in the NB85 group who after achievement of CR were consolidated with 3cCT had a 5-year PFS of 24% compared with 32% of those treated with MAT followed by ABMT (P = .5). CONCLUSION: Intensified therapy improves response rate and prolongs survival of children with disseminated neuroblastoma, although its impact on the eventual cure rate remains to be established.

Recombinant interferon-alpha 2A as maintenance treatment for patients with advanced stage chronic lymphocytic leukemia responding to chemotherapy.

Forty-five patients suffering from advanced B-CLL were randomized to receive interferon-alpha (IFN alpha) or no treatment after achieving complete remission or partial response, following a chemotherapy protocol called MiNa. The two groups were fully comparable in terms of clinical characteristics and level of response obtained by chemotherapy. IFN alpha was given at a dose of 3 megaunits three times a week intramuscularly for 1 year. The IFN-treated patient group showed a significantly longer duration of response and a less frequent incidence of infections as compared to the no treatment group. A minority of patients who had had partial response to chemotherapy obtained complete remission while on therapy with IFN alpha. Toxicity was mild and patient compliance was excellent. We conclude that IFN alpha may have a role as maintenance therapy in CLL for patients responding to chemotherapy.

Long-term results of a randomized trial comparing cisplatin with cisplatin and cyclophosphamide with cisplatin, cyclophosphamide, and adriamycin in advanced ovarian cancer. GICOG (Gruppo Interregionale Cooperativo Oncologico Ginecologia), Italy.

We report the long-term results of a randomized trial comparing cisplatin (P) with cisplatin and cyclophosphamide (CP) with cisplatin, cyclophosphamide, and adriamycin (CAP) in advanced ovarian cancer. Overall, this update confirms previously published data on 529 cases. Median survival times for the three treatments--CAP, CP, and P--are, respectively, 23, 20, and 19 months. The differences among the three arms are still nonsignificant and the estimated percentage survival at 7 years and confidence limits are, respectively, 21.7 (14.9-28.4), 17.0 (11.0-22.9), and 12.2 (6.9-17.4). According to the results of the Cox regression model on prognostic factors, higher grading, a larger residual tumor size, and performance status less than 80 (Karnovsky) all were independently associated with a poorer outcome, while a serous histotype was related to a better prognosis. The other variables (age, stage, center, type of surgery) initially included in the model did not appear to be significantly related to prognosis. The implications of these long-terms results relative to the application of combination chemotherapy with CAP or CP are discussed.

Bilateral breast involvement in a 71-year-old white man with lambda light chain disease. Regression after a new chemotherapy combination. A case report.

A rare case of lambda light chain disease with bilateral breast involvement is described. A complete regression after a new chemotherapy combination (peptichemio + teniposide + dexamethasone) was obtained. A previous treatment with prednisone + melphalan was ineffective.

Lung cancer: a review of current therapeutic modalities.

This article describes the current approach to the systematic management of both small cell and non-small cell lung cancer (NSCLC). The treatment of stages I, II, and IIIa NSCLC is surgical resection. Although adjuvant chemotherapy in stage I disease offers no survival benefit, the role of adjuvant chemotherapy in stage II and IIIa NSCLC remains controversial. Results of pilot studies using neoadjuvant chemotherapy in stage IIIa NSCLC are encouraging and data from ongoing randomized trials are awaited with interest. For locally advanced NSCLC, chest irradiation remains the standard of care. However, the addition of systemic chemotherapy holds promise. The impact of cisplatin-based regimens on overall survival in stage IV NSCLC remains disappointing. The introduction of newer agents, such as 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11), a topoisomerase-I inhibitor, has shown early favorable results. Chemotherapy is the most important therapeutic modality in the management of small cell lung cancer because of this cancer's propensity for early dissemination. In limited stage small cell lung cancer, chest radiotherapy, particularly if used early and concurrently with chemotherapy, may improve survival, but at the expense of increased toxicity. The role of prophylactic brain irradiation remains controversial in limited-stage disease. Chemotherapy is also the most important treatment modality in extensive-stage disease, but its role is only palliative. Radiotherapy is reserved primarily for disease-related complications in patients in whom chemotherapy has failed.

Combined modality therapy for small cell lung cancer.

Small cell carcinoma is one of the solid cancers for which chemotherapy is effective and can prolong the survival of patients. There is a general agreement that the standard regimen is PVP (cisplatin/etoposide) or alternating PVP-CAV (cyclophosphamide/doxorubicin/vincristine) therapy, replacing CAV, which had been considered standard. For the improvement of the treatment results of small cell carcinoma combined modality therapy including radiotherapy and/or surgery is essential, especially against limited disease. The effect of prophylactic cranial irradiation is obscure, because of the relapse to other sites of organs and the late complications of brain radiation. The present status of combined modality therapy for small cell carcinoma is reviewed and the future essential trials are discussed.

Alternating chemotherapy with cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PVP) against small cell lung cancer. Eastern Shikoku Lung Cancer Chemotherapy Group.

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.

A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study.

Six hundred eighty assessable patients with measureable stage III M1, non-small-cell lung cancer (NSCLC) were randomized to one of five treatment arms including cisplatin, etoposide (VP-16) +/- methylglyoxal bisguanylhydrazone (MGBG; PVp, PVpM); cisplatin, vinblastine (PVe); or PVe alternating with vinblastine, mitomycin (PVeMi); or fluorouracil, vincristine, mitomycin/cyclophosphamide, doxorubicin, cisplatin (FOMi/CAP). The overall response rate was 20% with 3% complete responses and 17% partial remissions. The duration of these responses was not statistically different by treatment regimen and varied from 2.7 months to 5.0 months. The overall median survival for all patients was 5.3 months and is not different by treatment. Toxicity was greater in PVpM. The similarity of results for response, duration of response, and survival does not establish the superiority of any of these platinum-based regimens for standard clinical usage.

[Cyclic high dose CAP therapy by short-stay admission for ovarian malignancies--to increase total dose of CDDP and to improve quality of life of patients].

Since 1986, attempts have been made to improve the anti-cancer effect of Cisplatin (CDDP) in malignant ovarian tumor patients and their quality of life (QOL), by increasing single and total dose of CDDP and by short-stay cyclic treatment at our institution. In this study, the side effects of CDDP at high and low doses were compared and the effect on the QOL was analysed. Twenty ovarian malignant tumor patients who underwent adjuvant chemotherapy (CDDP 70 mg/m2, Adriamycin (ADR) 20 mg/m2, Cyclophosphamide (CPM) 200 mg/m2 given every 4 weeks for a total of 5 times and every 8-12 weeks thereafter for 5 times) after initial surgery were compared with non randomized control patients who received the old regimen of of our institution (CDDP 35 mg/m2, ADR 20 mg/m2, CRP 200 mg/m2, 5-FU 150 mg/m2 for 5 days given every 4 weeks for a total of 5 times without discharge from hospital). There was no significant difference between the groups in the white blood cell (WBC) count and creatinine clearance (Ccr) throughout the treatment, although a slight drop was observed after the second course in both groups. The QOL was examined by interviewing the patients on their physical and mental condition. Although the total amount of CDDP was increased from 175 mg/m2 to as much as 700 mg/m2, no severe nephrotoxicity or myelosuppression was seen and patients felt better and preserved a good QOL during a short hospital stay. These results clearly indicate the efficacy of our new regimen.

Comparative study of combination chemotherapy of ovarian cancer: cyclophosphamide, adriamycin and cisplatin versus 5-fluorouracil, cyclophosphamide and mitomycin C.

CAP, a multiple-drug combination therapy using cyclophosphamide (750 mg/m2), adriamycin (20-30 mg/m2) and cisplatin (50-75 mg/m2), was applied to 69 cases of epithelial ovarian cancer. The results of this therapy were compared with those of FAM (involving 5-fluorouracil, cyclophosphamide and mitomycin C) in 47 cases of the same cancer, retrospectively. The 5-year survival rate was 61.6% for cases treated with CAP and 56.3% for cases treated with FAM. All 9 patients at stage Ia treated with CAP are free of disease, however, 3 patients out of 13 at stage Ia treated with FAM experienced a recurrence of the disease and died. In stage III and IV cases with detectable lesions, a response was observed in 61.3% (19/31) treated with CAP and in 10.5% (2/19) treated with FAM.