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Multidisciplinary Treatment for Advanced Nasopharyngeal Carcinoma
Auris·Nasus·Larynx (Tokyo) 12 (Supp!. II) S 244-S 248, 1985
MULTIDISCIPLINARY TREATMENT FOR ADVANCED NASOPHARYNGEAL CARCINOMA Hisao MIYASHITA, M.D., Yuzuru TANIKAWA, M.D., Kunihiko TSUTSUMIUCHI, M.D., Tomohiko NIGAURI, M.D., Tsuneo SASAKI, M.D., * and Tadayoshi MATSUDA, M.D. ** Departments of Otolaryngology, *Chemotherapy, and ** Radiology, Tokyo Metropolitan Komagome Hospital, Tokyo, 113 Japan
Of 30 nasopharyngeal carcinoma (NPC) cases seen from Jan. 1976 through Mar. 1984 at Tokyo Metropolitan Komagome Hospital, 19 previously untreated patients with more than I-year follow-up were retrospectively investigated to confirm the effective treatment modality. The average age was 51 years; the ratio of male to female was 3.5:1. Fifteen were in stage IV, 3 in stage III, and 1 in stage II. These 19 patients were grouped into three treatment modalities: a) radiation±unplanned chemotherapy (RT ± CM); b) radiation+unplanned cis-diamminedichloroplatinum (II) (CDDP)-based chemotherapy (RT+unplanned CDDP); and c) radiation+ planned CDDP-based chemotherapy (RT + planned CDDP). Planned CDDP-based chemotherapy consisted of 20--50 mg/M 2 CDDP, i.v. for 1 hr, 7.5-15 mg/body bleomycin (BLM), i.v. and/ or 20--30 mg/body MTX, i.v. at weekly intervals with diuresis for at least 4 courses. Plasma platinum (Pt) concentration before and 1 hr after CDDP administration revealed a gradual increase due to accumulated protein-bound Pt, while free Pt remained transient. This regimen could be safely administered for at least 4 courses. The survival rate of RT + planned CDDP (n= 8) was 100 % at maximum follow-up of 55 months, while RT±CM (n=6) at maximum follow-up of 54 months and RT+unplanned CDDP(n=5) at maximum follow-up of 38 months were 17 and 0%, respectively. Thus, we concluded that the most effective treatment modality for advanced NPC was RT+planned CDDP. Nasopharyngeal carcinoma (NPC) has been one of the worst prognostic malignancies in the head and neck, because symptoms often appear in a later stage with complications
such as cervical mass or cranial nerve involvement. Though radiotherapy is mandatory, there still have been difficulties in controlling primary lesions even by increased dosages. Furthermore, distant metastasis was frequently observed during treatment especially in bone, lung, liver, etc. (BEDWINEK et al., 1980). Since 1980, cis-diamminedichloroplatinum (II) (CDDP) has been introduced in Tokyo Metropolitan Komagome Hospital (TMKH), and combination chemotherapy has been tried for various head and neck cancers (RANDOLPH et al., 1978). In this series, we aimed to confirm the effective treatment modality of NPC by analyzing our treatment results retrospectively. Materials and Methods A total of 30 NPC patients was treated at TMKH from January 1976 through March 1984. Five patients with recurrence had prior treatment at other facilities, 3 had uncertain primary sites, one refused further treatment, and 2 were in the period less than 12 months after treatment. These 11 patients were excluded from the data. The remaining 19 previously untreated patients were grouped into three categories according to the treatment modalities: 1) radiation alone; when recurrence or metastasis occurred, combination chemotherapy without CDDP was occasionally scheduled (radiation ± unplanned chemotherapy); 2) radiation; when recur-
S 245
H. MIYASHITA et al.
rence or metastasis occurred, unplanned COOP-based chemotherapy was scheduled (radiation + unplanned COOP-based chemotherapy); and 3) radiation combined with planned COOP-based chemotherapy (radiation + planned COOP-based chemotherapy). All the patients were Japanese; the ratio of male to female was 3.5: 1. The ages ranged from 16 to 81 years with an average of 51 years (males 50 years and females 55 years). All were confirmed histologically at primary sites. The TNM classification and staging of these cases based on UICC in 1978 are summarized in Table 1. Most of them were in stage IV, 3 in stage III, and one in stage II. Among them, 3 patients had distant metastasis at the beginning of treatment. Histologically, 11 cases revealed non-keratinizing epidermoid carcinoma, 7 undifferentiated carcinoma, and only one well keratinized epidermoid carcinoma (sq.ca).
from 50 to 70 Gy for 5 to 7 weeks with parallel opposing portals, encompassing the primary lesion and the upper portion of the neck. A single anterior portal was utilized to cover the lower portion of the neck, both supraclavicular areas, and the upper mediastinum (MESIC et al., 1981). When indicated, wedge filters, differential loadings, shrinking field techniques, and conformational field techniques were employed (Fig. 1). Electrons generated by Betatron were boosted if necessary. Since 1980, the so-called multidisciplinary treatment modality combining extensive radiotherapy with planned COOP-based chemotherapy has been applied. Planned CDDP-Based Chemotherapy
Radiotherapy
These patients underwent radiotherapy of 4 Mev X-ray with the tumor dose ranging
Before chemotherapy, a general check-up, especially creatinine clearance, was routinely carried out in all patients and audiograms were performed in selected cases. Twenty to 50 mg/M2 COOP i.v. for one hour infusion with 7.5-15 mg/body bleomycin, and/or 20-30 mg/body methotrexate i.v. in one shot at weekly intervals for 4 to 6
Table 1. Cases of nasopharyngeal cancer (1976. 1-1984. 3, TMKH). No.
Name Age
Sex
TNM
Radiation ± unplanned chemotherapy 1 N.B. 50 M T2N2 MO 2 T.H. 64 M TaN 2Mo 3 16 U.R. F T,NaMo 4 O.K. 70 F T.NaM, 5 M.T. 42 M T2N2 MO K.Y. 45 6 M T.NoM, Radiation + unplanned chemotherapy* T.H. 43 M 7 T2N2 MO 63 M 8 S.A. T.N.M , S.M. 81 F TaN,Mo 9 10 45 M S.S. T.NsMo M 11 U.K. 39 T2 N OMo Radiation+planned chemotherapy* N.A. 26 M 12 T.NoMo M A.H. 47 13 TsN2 MO T.K. F T.N1M o 14 53 15 M.T. 66 M T.N,M o 16 A.T. M 37 T2N,Mo M 17 U.M. 71 T3N,MO M 18 M.I. 51 T.NaMo 19 S.S. M T.N,M o 57 * CDDP-based.
Stage
Histology
IV IV IV IV IV IV
non-kera. epid. ca. undiff. ca. undiff. ca. non-kera. epid. ca. non-kera. epid. ca. non-kera. epid. ca.
EX· VCR·ADR·NTX·BLM BLM·MMC
IV IV III IV
non-kera. epid. ca. non-kera. epid. ca. sq. ca. non-kera. epid. ca. non-kera. epid. ca.
BLM·MMC·CDDP·EX·ADM BLM·CDDP BLM·CDDP BLM·CDDP MTX·CDDP·BLM·VCR
non-kera. epid. ca. undiff. ca. undiff. ca. undiff. ca. undiff. ca. non-kera. epid. ca. undiff. ca. non-kera. epid. ca.
CDDp·MTX CDDP·BLM CDDP·BLM·MTX CDDp·MTX CDDP·BLM CDDP·BLM CDDP·BLM·MTX CDDP·BLM·MTX
II
IV IV IV IV III III
IV IV
Drug EX·BLM·CQ
S 246
H. MIYASHITA et
at.
a)
_ _1ii11i¥ ------------'1----
c)
me_ _ _ lflflf
_jJ.jJ.jJ.jJ.
_
--.,r-- ,Hilf
: RADIATION
.u. : CHEMOTHERAPY
COOP ; 20 - S()IlI( /MI
SU.I
"d!O' MTX
-------
(l.v.
101
It. )
1 S- Ullltl bl)dy. ( '~ Id I V,)
: 16 - 101IIt/boOy. (',I:>id I.V)
I I
'Nnkly
Fig. 2. Modalities of planned CDDP based chemotherapy.
MPS-3 reservoir to detect free and proteinbound Pt concentration in the same way described above.
Fig. 1. Case 14 (T.K., 53, F) liniac graphy.
courses were administered. Furosemide and steroid were used intravenously on day 1 and day 2 (SASAKI et at., 1982). One of the following three therapeutic conditions was selected: a) simultaneous chemotherapy at the latter half of the radiotherapy ; b) prior chemotherapy followed by radiotherapy; c) radiotherapy followed by chemotherapy. Most patients followed this procedure. In one case of prior chemotherapy, severe mucositis was encountered at the earlier stage of radiotherapy, probably due to bleomycin. Thereafter, this combination was not utilized. Boosted COOP-based chemotherapy was also performed in most cases (Fig. 2). Plasma Platinum (Pt) Concentration after CDDP-Based Chemotherapy Patients' plasma just before and one hour after the completion of COOP infusion was collected as soon as possible. As the initial experiment, the total plasma Pt concentration was measured by flameless atomic absorption spectrometry (Hitachi, 170-70) at NAC Co., Japan. As the next experiment, each plasma sample was centrifuged by means of an Amicon
Results Of 19 patients, 9 are alive without primary disease. Survival periods ranged from 12 to 53 months. All patients belonged to the radiotherapy with planned COOP-based chemotherapy group except one who received radiotherapy alone. In spite of the controlled primary lesion, 2 of 8 in the radiotherapy with planned COOPbased chemotherapy group have been alive with distant metastatic diseases of lung and bone for 23 and 25 months, respectively. Survival rates among these three groups are depicted in Fig. 3 according to KaplanMeier's method. Radiotherapy with planned COOP-based chemotherapy was distinctively demonstrated to be the best treatment modality (p
H. MIYASHITA et al. (%)
100 90 80 w I- 10
« a:: 60 ...J « 50 > > 40
a:: :> 30 I/)
(RAOiATlON+planned coOP based CHEMOTHERAPY) (n=8)
j &j
I
:
l-.
I : 6-·_· ...h ....j
,
c}-._._.,
.................. ~ ..................... .
~.-.-.4- . -.---.. ,
I
i .-._._._._._.,._-_._-_._------0
, ..............................10 ...... --------... - ... ,
20 10 0
S 247
(RAOIATlON'cunplanned CHEMOTHERAPY) (n=6)
(RAOIATlON+unplann.d COOP based CHEMOTHERAPY) (n=5) I
10
30
20
40
50 (month)
Fig. 3. Comparison of survival rate of nasopharyngeal carcinoma (Kaplan-Meier) (1976.11985.3, TMKH).
(Week)
Fig. 4. Free and bound Pt concentration in plasma.
but also in head and neck carcinoma. However, the evaluation of effectiveness in different malignancy sites is difficult. To discuss the same etiological malignancies, we selected NPC which was treated with radiation and/or chemotherapy. In our series, radiotherapy followed by planned CDDP-based chemotherapy was considered to be the most useful modality for NPC. Whether radiotherapy should be the first treatment to start with or not is still debatable (DECKER et al., 1983). If no metastatic lesion is detectable, radiotherapy can be used for sufficient local control without interruption caused by chemotherapeutic disadvantages. As far as our regimen was concerned, intravenous administration of CDDP-based chemotherapy at weekly intervals was safely carried out for at least 4 courses, whenever
patients had no hematological or nephrological disturbance. Bleomycin should be excluded if pulmonary dysfunction is a worry, especially in aged patients. The plasma Pt concentration accumulated for longer periods by weekly administration of CDDP in contrast to the rapid turnover of free Pt in plasma. Thus we concluded that extensive radiotherapy followed by planned CDDP-based chemotherapy was the most relevant treatment modality for advanced NPC. References BEDWINEK, J.M., PEREZ, C.A., and KEYS, D.J.: Analysis of failures after definitive irradiation for epidermoid carcinoma of the nasopharynx. Cancer 45: 2725-2729, 1980. DECKER, D.A., DRELICHMAN, A., AL-SARRAF, M., CRISSMAN, J., and REED, M.L.: Chemotherapy for nasopharyngeal carcinoma. Cancer 52: 602-605, 1983. HORIUCHI, M., INUYAMA, Y., KOHNO, N., MASHINO, S., and FUJII, M.: Pharmacokinetics of cisdechlorodiammineplatinum (II). Gan to Kagakuryoho 9: 632-637, 1982. MAITOX, D., STERNSON, L.A., VON HOFF, D.D., KUHN, J.G., and REPTA, A.J.: Tumor concentration of platinum in patients with head and neck cancer. Otolaryngol. Head Neck Surg. 91: 271-275, 1983. MESIC, J.B., FLETCHER, G.H., and GOEPFERT, H.: Megavoltage irradiation of epithelial tumors of the nasopharynx. Int. J. Radiat. Oncol. BioI. Phys. 7: 447-453, 1981. RANDOLPH, V.L., VALLEJO, A., SPIRO, R.H., SHAH,J., STRONG, E.W., Huvos, A.G., and WIITES, R.E.: Combination therapy of advanced head and neck cancer. Cancer 41: 460-467,1978.
S 248
H. MIYASHITA
SASAKI, T., IBUKA, T., IMAI, K., SAKAI, KAWA,
M.,
TANIKAWA,
Y.,
Y., HAYA-
MIYASHITA,
H.,
KOMIYA, Y., and MATSUDA, T.: Combination chemotherapy with cis-diamminedichloropla-
et at.
tinum (II) and bleomycin in advanced head and neck cancer. Gan to Kagakuryoho 9: 1412-1417, 1982.
MULTIDISCIPLINARY TREATMENT FOR ADVANCED NASOPHARYNGEAL CARCINOMA Hisao MIYASHITA, M.D., Yuzuru TANIKAWA, M.D., Kunihiko TSUTSUMIUCHI, M.D., Tomohiko NIGAURI, M.D., Tsuneo SASAKI, M.D., * and Tadayoshi MATSUDA, M.D. ** Departments of Otolaryngology, *Chemotherapy, and ** Radiology, Tokyo Metropolitan Komagome Hospital, Tokyo, 113 Japan
Of 30 nasopharyngeal carcinoma (NPC) cases seen from Jan. 1976 through Mar. 1984 at Tokyo Metropolitan Komagome Hospital, 19 previously untreated patients with more than I-year follow-up were retrospectively investigated to confirm the effective treatment modality. The average age was 51 years; the ratio of male to female was 3.5:1. Fifteen were in stage IV, 3 in stage III, and 1 in stage II. These 19 patients were grouped into three treatment modalities: a) radiation±unplanned chemotherapy (RT ± CM); b) radiation+unplanned cis-diamminedichloroplatinum (II) (CDDP)-based chemotherapy (RT+unplanned CDDP); and c) radiation+ planned CDDP-based chemotherapy (RT + planned CDDP). Planned CDDP-based chemotherapy consisted of 20--50 mg/M 2 CDDP, i.v. for 1 hr, 7.5-15 mg/body bleomycin (BLM), i.v. and/ or 20--30 mg/body MTX, i.v. at weekly intervals with diuresis for at least 4 courses. Plasma platinum (Pt) concentration before and 1 hr after CDDP administration revealed a gradual increase due to accumulated protein-bound Pt, while free Pt remained transient. This regimen could be safely administered for at least 4 courses. The survival rate of RT + planned CDDP (n= 8) was 100 % at maximum follow-up of 55 months, while RT±CM (n=6) at maximum follow-up of 54 months and RT+unplanned CDDP(n=5) at maximum follow-up of 38 months were 17 and 0%, respectively. Thus, we concluded that the most effective treatment modality for advanced NPC was RT+planned CDDP. Nasopharyngeal carcinoma (NPC) has been one of the worst prognostic malignancies in the head and neck, because symptoms often appear in a later stage with complications
such as cervical mass or cranial nerve involvement. Though radiotherapy is mandatory, there still have been difficulties in controlling primary lesions even by increased dosages. Furthermore, distant metastasis was frequently observed during treatment especially in bone, lung, liver, etc. (BEDWINEK et al., 1980). Since 1980, cis-diamminedichloroplatinum (II) (CDDP) has been introduced in Tokyo Metropolitan Komagome Hospital (TMKH), and combination chemotherapy has been tried for various head and neck cancers (RANDOLPH et al., 1978). In this series, we aimed to confirm the effective treatment modality of NPC by analyzing our treatment results retrospectively. Materials and Methods A total of 30 NPC patients was treated at TMKH from January 1976 through March 1984. Five patients with recurrence had prior treatment at other facilities, 3 had uncertain primary sites, one refused further treatment, and 2 were in the period less than 12 months after treatment. These 11 patients were excluded from the data. The remaining 19 previously untreated patients were grouped into three categories according to the treatment modalities: 1) radiation alone; when recurrence or metastasis occurred, combination chemotherapy without CDDP was occasionally scheduled (radiation ± unplanned chemotherapy); 2) radiation; when recur-
S 245
H. MIYASHITA et al.
rence or metastasis occurred, unplanned COOP-based chemotherapy was scheduled (radiation + unplanned COOP-based chemotherapy); and 3) radiation combined with planned COOP-based chemotherapy (radiation + planned COOP-based chemotherapy). All the patients were Japanese; the ratio of male to female was 3.5: 1. The ages ranged from 16 to 81 years with an average of 51 years (males 50 years and females 55 years). All were confirmed histologically at primary sites. The TNM classification and staging of these cases based on UICC in 1978 are summarized in Table 1. Most of them were in stage IV, 3 in stage III, and one in stage II. Among them, 3 patients had distant metastasis at the beginning of treatment. Histologically, 11 cases revealed non-keratinizing epidermoid carcinoma, 7 undifferentiated carcinoma, and only one well keratinized epidermoid carcinoma (sq.ca).
from 50 to 70 Gy for 5 to 7 weeks with parallel opposing portals, encompassing the primary lesion and the upper portion of the neck. A single anterior portal was utilized to cover the lower portion of the neck, both supraclavicular areas, and the upper mediastinum (MESIC et al., 1981). When indicated, wedge filters, differential loadings, shrinking field techniques, and conformational field techniques were employed (Fig. 1). Electrons generated by Betatron were boosted if necessary. Since 1980, the so-called multidisciplinary treatment modality combining extensive radiotherapy with planned COOP-based chemotherapy has been applied. Planned CDDP-Based Chemotherapy
Radiotherapy
These patients underwent radiotherapy of 4 Mev X-ray with the tumor dose ranging
Before chemotherapy, a general check-up, especially creatinine clearance, was routinely carried out in all patients and audiograms were performed in selected cases. Twenty to 50 mg/M2 COOP i.v. for one hour infusion with 7.5-15 mg/body bleomycin, and/or 20-30 mg/body methotrexate i.v. in one shot at weekly intervals for 4 to 6
Table 1. Cases of nasopharyngeal cancer (1976. 1-1984. 3, TMKH). No.
Name Age
Sex
TNM
Radiation ± unplanned chemotherapy 1 N.B. 50 M T2N2 MO 2 T.H. 64 M TaN 2Mo 3 16 U.R. F T,NaMo 4 O.K. 70 F T.NaM, 5 M.T. 42 M T2N2 MO K.Y. 45 6 M T.NoM, Radiation + unplanned chemotherapy* T.H. 43 M 7 T2N2 MO 63 M 8 S.A. T.N.M , S.M. 81 F TaN,Mo 9 10 45 M S.S. T.NsMo M 11 U.K. 39 T2 N OMo Radiation+planned chemotherapy* N.A. 26 M 12 T.NoMo M A.H. 47 13 TsN2 MO T.K. F T.N1M o 14 53 15 M.T. 66 M T.N,M o 16 A.T. M 37 T2N,Mo M 17 U.M. 71 T3N,MO M 18 M.I. 51 T.NaMo 19 S.S. M T.N,M o 57 * CDDP-based.
Stage
Histology
IV IV IV IV IV IV
non-kera. epid. ca. undiff. ca. undiff. ca. non-kera. epid. ca. non-kera. epid. ca. non-kera. epid. ca.
EX· VCR·ADR·NTX·BLM BLM·MMC
IV IV III IV
non-kera. epid. ca. non-kera. epid. ca. sq. ca. non-kera. epid. ca. non-kera. epid. ca.
BLM·MMC·CDDP·EX·ADM BLM·CDDP BLM·CDDP BLM·CDDP MTX·CDDP·BLM·VCR
non-kera. epid. ca. undiff. ca. undiff. ca. undiff. ca. undiff. ca. non-kera. epid. ca. undiff. ca. non-kera. epid. ca.
CDDp·MTX CDDP·BLM CDDP·BLM·MTX CDDp·MTX CDDP·BLM CDDP·BLM CDDP·BLM·MTX CDDP·BLM·MTX
II
IV IV IV IV III III
IV IV
Drug EX·BLM·CQ
S 246
H. MIYASHITA et
at.
a)
_ _1ii11i¥ ------------'1----
c)
me_ _ _ lflflf
_jJ.jJ.jJ.jJ.
_
--.,r-- ,Hilf
: RADIATION
.u. : CHEMOTHERAPY
COOP ; 20 - S()IlI( /MI
SU.I
"d!O' MTX
-------
(l.v.
101
It. )
1 S- Ullltl bl)dy. ( '~ Id I V,)
: 16 - 101IIt/boOy. (',I:>id I.V)
I I
'Nnkly
Fig. 2. Modalities of planned CDDP based chemotherapy.
MPS-3 reservoir to detect free and proteinbound Pt concentration in the same way described above.
Fig. 1. Case 14 (T.K., 53, F) liniac graphy.
courses were administered. Furosemide and steroid were used intravenously on day 1 and day 2 (SASAKI et at., 1982). One of the following three therapeutic conditions was selected: a) simultaneous chemotherapy at the latter half of the radiotherapy ; b) prior chemotherapy followed by radiotherapy; c) radiotherapy followed by chemotherapy. Most patients followed this procedure. In one case of prior chemotherapy, severe mucositis was encountered at the earlier stage of radiotherapy, probably due to bleomycin. Thereafter, this combination was not utilized. Boosted COOP-based chemotherapy was also performed in most cases (Fig. 2). Plasma Platinum (Pt) Concentration after CDDP-Based Chemotherapy Patients' plasma just before and one hour after the completion of COOP infusion was collected as soon as possible. As the initial experiment, the total plasma Pt concentration was measured by flameless atomic absorption spectrometry (Hitachi, 170-70) at NAC Co., Japan. As the next experiment, each plasma sample was centrifuged by means of an Amicon
Results Of 19 patients, 9 are alive without primary disease. Survival periods ranged from 12 to 53 months. All patients belonged to the radiotherapy with planned COOP-based chemotherapy group except one who received radiotherapy alone. In spite of the controlled primary lesion, 2 of 8 in the radiotherapy with planned COOPbased chemotherapy group have been alive with distant metastatic diseases of lung and bone for 23 and 25 months, respectively. Survival rates among these three groups are depicted in Fig. 3 according to KaplanMeier's method. Radiotherapy with planned COOP-based chemotherapy was distinctively demonstrated to be the best treatment modality (p
H. MIYASHITA et al. (%)
100 90 80 w I- 10
« a:: 60 ...J « 50 > > 40
a:: :> 30 I/)
(RAOiATlON+planned coOP based CHEMOTHERAPY) (n=8)
j &j
I
:
l-.
I : 6-·_· ...h ....j
,
c}-._._.,
.................. ~ ..................... .
~.-.-.4- . -.---.. ,
I
i .-._._._._._.,._-_._-_._------0
, ..............................10 ...... --------... - ... ,
20 10 0
S 247
(RAOIATlON'cunplanned CHEMOTHERAPY) (n=6)
(RAOIATlON+unplann.d COOP based CHEMOTHERAPY) (n=5) I
10
30
20
40
50 (month)
Fig. 3. Comparison of survival rate of nasopharyngeal carcinoma (Kaplan-Meier) (1976.11985.3, TMKH).
(Week)
Fig. 4. Free and bound Pt concentration in plasma.
but also in head and neck carcinoma. However, the evaluation of effectiveness in different malignancy sites is difficult. To discuss the same etiological malignancies, we selected NPC which was treated with radiation and/or chemotherapy. In our series, radiotherapy followed by planned CDDP-based chemotherapy was considered to be the most useful modality for NPC. Whether radiotherapy should be the first treatment to start with or not is still debatable (DECKER et al., 1983). If no metastatic lesion is detectable, radiotherapy can be used for sufficient local control without interruption caused by chemotherapeutic disadvantages. As far as our regimen was concerned, intravenous administration of CDDP-based chemotherapy at weekly intervals was safely carried out for at least 4 courses, whenever
patients had no hematological or nephrological disturbance. Bleomycin should be excluded if pulmonary dysfunction is a worry, especially in aged patients. The plasma Pt concentration accumulated for longer periods by weekly administration of CDDP in contrast to the rapid turnover of free Pt in plasma. Thus we concluded that extensive radiotherapy followed by planned CDDP-based chemotherapy was the most relevant treatment modality for advanced NPC. References BEDWINEK, J.M., PEREZ, C.A., and KEYS, D.J.: Analysis of failures after definitive irradiation for epidermoid carcinoma of the nasopharynx. Cancer 45: 2725-2729, 1980. DECKER, D.A., DRELICHMAN, A., AL-SARRAF, M., CRISSMAN, J., and REED, M.L.: Chemotherapy for nasopharyngeal carcinoma. Cancer 52: 602-605, 1983. HORIUCHI, M., INUYAMA, Y., KOHNO, N., MASHINO, S., and FUJII, M.: Pharmacokinetics of cisdechlorodiammineplatinum (II). Gan to Kagakuryoho 9: 632-637, 1982. MAITOX, D., STERNSON, L.A., VON HOFF, D.D., KUHN, J.G., and REPTA, A.J.: Tumor concentration of platinum in patients with head and neck cancer. Otolaryngol. Head Neck Surg. 91: 271-275, 1983. MESIC, J.B., FLETCHER, G.H., and GOEPFERT, H.: Megavoltage irradiation of epithelial tumors of the nasopharynx. Int. J. Radiat. Oncol. BioI. Phys. 7: 447-453, 1981. RANDOLPH, V.L., VALLEJO, A., SPIRO, R.H., SHAH,J., STRONG, E.W., Huvos, A.G., and WIITES, R.E.: Combination therapy of advanced head and neck cancer. Cancer 41: 460-467,1978.
S 248
H. MIYASHITA
SASAKI, T., IBUKA, T., IMAI, K., SAKAI, KAWA,
M.,
TANIKAWA,
Y.,
Y., HAYA-
MIYASHITA,
H.,
KOMIYA, Y., and MATSUDA, T.: Combination chemotherapy with cis-diamminedichloropla-
et at.
tinum (II) and bleomycin in advanced head and neck cancer. Gan to Kagakuryoho 9: 1412-1417, 1982.